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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified August 2014 by AIDS Malignancy Clinical Trials Consortium
Sponsor:
Collaborators:
The EMMES Corporation
Information provided by (Responsible Party):
AIDS Malignancy Clinical Trials Consortium
ClinicalTrials.gov Identifier:
NCT02059499
First received: February 7, 2014
Last updated: August 27, 2014
Last verified: August 2014

February 7, 2014
August 27, 2014
March 2014
June 2016   (final data collection date for primary outcome measure)
  • Proportion of participants achieving complete response (Arm A and B) [ Time Frame: At week 20 ] [ Designated as safety issue: No ]
    For each treatment comparison (imiquimod vs observation and fluorouracil vs observation) the proportions will be compared across sites using stratified Mantel-Haenszel-Cochran tests at the one-sided 0.025 alpha level.
  • Proportion of participants with spontaneous regression (Arm C) [ Time Frame: At week 20 ] [ Designated as safety issue: No ]
    For each treatment comparison (imiquimod vs observation and fluorouracil vs observation) the proportions will be compared across sites using stratified Mantel-Haenszel-Cochran tests at the one-sided 0.025 alpha level.
  • Presence of intra-anal HSIL on cytology or histology [ Time Frame: At week 20 ] [ Designated as safety issue: No ]
    Perianal HSIL will be descriptively reported separately, as well as combined.
Same as current
Complete list of historical versions of study NCT02059499 on ClinicalTrials.gov Archive Site
  • Incidence of adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to week 44 ] [ Designated as safety issue: Yes ]
    To examine the tolerability and safety of the three arms, descriptive statistics for adverse events will be computed. Adverse events will be summarized at the event level and participant level according to severity. Adverse events will be stratified according to those reported at or before week 20 and after week 20. Proportions and their exact 95% confidence intervals will be calculated. Summary statistics will be computed for the amount of study drug taken.
  • Proportion of participants achieving complete response or spontaneous regression [ Time Frame: Up to week 44 ] [ Designated as safety issue: No ]
    Proportions will be compared across sites using the stratified Mantel-Haenszel-Cochran test at the two-sided 0.05 alpha level.
  • Number of quadrants with HSIL found on biopsies [ Time Frame: Up to week 48 ] [ Designated as safety issue: No ]
    Will be compared between arms treating the response as an ordinal variable.
  • Proportion of patients achieving complete or partial responses [ Time Frame: Up to week 44 ] [ Designated as safety issue: No ]
    The proportion of patients achieving complete or partial responses with imiquimod or fluorouracil will be compared to observation only.
  • Persistence of HPV type specific infections [ Time Frame: At week 20 ] [ Designated as safety issue: No ]
    The frequency and proportion of HPV types present at baseline that are no longer detected at week 20 will be reported. The frequency and proportion of new HPV infections detected at week 20 that were not present at baseline will also be reported. Proportions and their exact binomial 95% confidence intervals will be calculated.
  • Presence of intra-anal HSIL on cytology or histology [ Time Frame: At week 44 ] [ Designated as safety issue: No ]
    Perianal HSIL will be descriptively reported separately, as well as combined. Results for the observation arm will be stratified into cross-over treatment groups.
Same as current
Not Provided
Not Provided
 
Imiquimod, Fluorouracil, or Observation in Treating Patients With High-Grade Anal Squamous Skin Lesions Who Are HIV-Positive
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

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.

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
  • Anal Intraepithelial Neoplasia
  • High-grade Squamous Intraepithelial Lesion
  • HIV Infection
  • Drug: imiquimod
    Given intra-anally
    Other Names:
    • Aldara
    • IMQ
    • R 837
  • Drug: fluorouracil
    Given intra-anally
    Other Names:
    • 5-fluorouracil
    • 5-Fluracil
    • 5-FU
  • Other: questionnaire administration
    Ancillary studies
  • Other: laboratory biomarker analysis
    Correlative studies
  • Experimental: Arm A (imiquimod)
    Patients apply imiquimod intra-anally QD for 16 weeks.
    Interventions:
    • Drug: imiquimod
    • Other: questionnaire administration
    • Other: laboratory biomarker analysis
  • Experimental: Arm B (fluorouracil)
    Patients apply fluorouracil intra-anally BID on days 1-5. Treatment repeats every 2 weeks for 8 courses in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Drug: fluorouracil
    • Other: questionnaire administration
    • Other: laboratory biomarker analysis
  • No Intervention: Arm C (observation)
    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.
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Not yet recruiting
150
December 2016
June 2016   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • HIV-positive; documentation of HIV infection must be based on a federally approved, licensed HIV test performed in conjunction with screening (enzyme linked immunosorbent assay [ELISA], western blot, or other test); alternatively, this documentation may include a record that another physician has documented that the patient has HIV based on prior ELISA and western blot; 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
  • Biopsy-proven HSIL (anal intraepithelial neoplasia 2 (AIN2) and/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 1 week prior to enrollment
  • HSIL occupies at least 25% of the circumference of the anal canal at either the squamocolumnar junction or distal anus on high-resolution anoscopy (HRA) at screening or entry based on available biopsy results and visual appearance
  • Anal HSIL lesions are visible at study entry 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 of >= 70%
  • Cluster of differentiation (CD)4 count >= 200 within 120 days prior to enrollment or plasma HIV-1 ribonucleic acid (RNA) < 200 copies/mL within 120 days prior to enrollment
  • For females, cervical cytology (if having a cervix) and gynecologic evaluation within 12 months prior to enrollment
  • Absolute neutrophil count (ANC) > 750 cells/mm^3 within 90 days prior to enrollment
  • Hemoglobin >= 9.0 g/dL within 90 days prior to enrollment
  • Platelet count >= 75,000/mm^3 within 90 days prior to enrollment

Exclusion Criteria:

  • History of anal cancer
  • Prior intra-anal use of topical 5-fluorouracil 5% or imiquimod 2.5%, 3.75% or 5% at any point, or use of perianal imiquimod 2.5%, 3.75% or 5% or topical 5-fluorouracil 5% within 6 months prior to enrollment
  • 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)
  • 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 study entry
  • Malignancy requiring systemic therapy; note: Kaposi's sarcoma limited to the skin is not exclusionary unless requiring systemic chemotherapy
  • Concurrent systemic corticosteroids, cytokines, and immunomodulatory therapy (e.g. interferons)
  • Prior history of HPV vaccination
  • Treatment for anal or perianal HSIL, low-grade squamous intraepithelial lesion (LSIL) or condyloma within 4 months of entry; 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 initiating study treatment; 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)
Both
27 Years and older
No
United States
 
NCT02059499
AMC-088, NCI-2013-02288, AMC-088, AMC-088, U01CA121947
Yes
AIDS Malignancy Clinical Trials Consortium
AIDS Malignancy Clinical Trials Consortium
  • National Cancer Institute (NCI)
  • The EMMES Corporation
Principal Investigator: Timothy Wilkin AIDS Associated Malignancies Clinical Trials Consortium
AIDS Malignancy Clinical Trials Consortium
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP