Imiquimod, Fluorouracil, or Observation in Treating Patients with High-Grade Anal Squamous Skin Lesions Who Are HIV-Positive
- 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) (at least two different medications) 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
- 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 7 days prior to randomization
- HSIL comprising 2 or more lesions, or anal HSIL in at least 2 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
- Anal HSIL lesions are visible at randomization and no lesions are suspicious for invasive cancer
- Ability to understand and willing to provide informed consent
- Participants must, in the opinion of the Investigator, be capable of complying with the requirements of this protocol including self-administration of study treatment
- Karnofsky performance status (KPS) of >= 70% or Eastern Cooperative Oncology Group (ECOG) performance status =< 1
- 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
- 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
- Absolute neutrophil count (ANC) > 750 cells/mm^3 within 90 days prior to randomization
- Hemoglobin >= 9.0 g/dL within 90 days prior to randomization
- Platelet count >= 75,000/mm^3 within 90 days prior to randomization
- History of anal cancer
- Prior intra-anal use of topical 5-fluorouracil 5% or imiquimod 2.5%, 3.75% or 5% for treatment of HSIL at any point, use of intra-anal or topical 5-fluorouracil 5% or imiquimod 2.5%, 3.75% or 5% for treatment of condyloma within 6 months prior to randomization or perianal imiquimod 2.5%, 3.75% or 5% or topical 5-fluorouracil 5% within 6 months prior to randomization
- Extensive concurrent perianal or lower vulvar HSIL or condyloma requiring a different treatment modality than the study treatment, or treatment that cannot be deferred in observation arm, per examining provider
- Condyloma occupying more than 50% of the circumference of the anal canal or that obscures a satisfactory exam
- Ongoing use of anticoagulant therapy other than aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) that places the participant at increased bleeding risk in the opinion of the site investigator
- Acute treatment for an infection (excluding fungal infection of the skin and sexually transmitted infections) or other serious medical illness within 14 days prior to randomization
- Malignancy requiring systemic therapy; Note: Kaposi sarcoma limited to the skin is not exclusionary unless requiring systemic chemotherapy
- Concurrent systemic corticosteroids, cytokines, and immunomodulatory therapy (e.g. interferons)
- Participants who received investigational agents, other than investigational antiretroviral agents for HIV, within the 4 weeks before randomization, unless approved by the study chair
- Treatment for anal or perianal HSIL, low-grade squamous intraepithelial lesion (LSIL) or condyloma within 4 months of randomization; please note that infrared coagulation (IRC) or electrocautery of a biopsy site to stop bleeding does not constitute treatment
- Female participants who are pregnant or breastfeeding; women of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to randomization; all women of childbearing potential must be willing to comply with an acceptable birth control regimen to prevent pregnancy while receiving treatment and for 3 months after treatment is discontinued as determined by the Investigator; post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential; (note: a woman of childbearing potential is one who is biologically capable of becoming pregnant; this includes women who are using contraceptives or whose sexual partners are either sterile or using contraceptives)
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 imiquimod 2.5% for treatment of anal HSIL compared to observation only.
III. To assess the efficacy of intra-anal topical 5-fluorouracil (fluorouracil) 5% for treatment of anal HSIL compared to observation only.
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. 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 courses 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.
After completion of study treatment, patients are followed up at weeks 20, 24, 26, 32, 40, and 44.
Trial Phase Phase III
Trial Type Treatment
AIDS Malignancy Consortium
Timothy James Wilkin
- Primary ID AMC-088
- Secondary IDs NCI-2013-02288
- Clinicaltrials.gov ID NCT02059499