Anal Intraepithelial NeoplasiaPhase 3NCT02059499
Imiquimod, Fluorouracil, or Observation in Treating HIV-Positive Patients With High-Grade Anal Squamous Skin Lesions
A Phase 3 study testing imiquimod, fluorouracil and questionnaire administration in people with Anal Intraepithelial Neoplasia and High-grade Squamous Intraepithelial Lesion, run by AIDS Malignancy Consortium at 13 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Anal Intraepithelial Neoplasia, High-grade Squamous Intraepithelial Lesion, HIV Infection
- What is being tested?
- imiquimod, fluorouracil and questionnaire administration
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 91 participants
- Where
- 13 sitesin 2 countries
- Study dates
- 28 Dec 2015to 2 May 2024
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 12Show fewer
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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)
Trial locations and contacts
13 sites in 2 countries.
13 sites in 2 countries
United States12 sites
Emory University
Atlanta, Georgia, 30303
Boston Medical Center
Boston, Massachusetts, 02118
UCLA CARE Center
Los Angeles, California, 90035
Louisiana State University Health Sciences Center - New Orleans
New Orleans, Louisiana, 70112
Laser Surgery Care
New York, New York, 10011
Cornell Clinical Trials Unit, New York Presbyterian Hospital
New York, New York, 10065
Weill Medical College of Cornell University
New York, New York, 10065
UCSF-Mount Zion
San Francisco, California, 94115
University of California, San Francisco
San Francisco, California, 94143
Benaroya Research Institute at Virginia Mason Medical Center
Seattle, Washington, 98101
Montefiore Medical Center
The Bronx, New York, 10461
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
About this study
Official title: 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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- 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.
- Being tested
- imiquimod, fluorouracil, questionnaire administration, laboratory biomarker analysis
- Medical subject headings
- Squamous Intraepithelial Lesions, HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
imiquimodDrug
Also called Aldara, IMQ, R 837
Given intra-anally
fluorouracilDrug
Also called 5-fluorouracil, 5-Fluracil, 5-FU
Given intra-anally
questionnaire administrationOther
Ancillary studies
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Arm A (imiquimod) | Experimental | Patients apply imiquimod intra-anally QD for 16 weeks. Receives: Drug: imiquimod; Other: questionnaire administration; Other: laboratory biomarker analysis |
| Arm B (fluorouracil) | Experimental | 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. Receives: Drug: fluorouracil; Other: questionnaire administration; Other: laboratory biomarker analysis |
| Arm C (observation) | No intervention | 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants Achieving Complete Response in 5-FU Arm and Observation Arm Using ITT Population
Complete response is defined as the absence of HSIL histology for all biopsies and the absence of HSIL cytology.
The percentage of participants achieving complete response in the 5-FU and observation arms will be reported and compared across sites, along with the corresponding p-value, using stratified Mantel-Haenszel-Cochran tests at a one-sided alpha level of 0.025.
Measured: At week 20
Percentage of Participants Achieving Complete Response (5-FU vs Observation ) Using Per Protocol Population
Complete response is defined as the absence of HSIL histology for all biopsies and the absence of HSIL cytology.
The percentage of participants achieving complete response in the 5-FU and observation arms will be reported, along with the corresponding p-value, using stratified Mantel-Haenszel-Cochran tests to compare results across sites at a one-sided alpha level of 0.025.
Measured: At week 20
Percentage of Participants Achieving Complete Response in 5-FU vs. Imiquimod, Using the ITT Population Restricted to Those Randomized to Either Treatment Prior to the Closure of the Imiquimod Arm.
Complete response is defined as an absence of HSIL histology for all biopsies and the absence of HSIL cytology.
Compare the percentage of complete response in 5-FU vs Imiquimod arms across sites using stratified CMH test at one-sided 0.05 alpha.
Measured: Week 20
Percentage of Participants Achieving Complete Response in 5-FU vs. Imiquimod, Using the PP Population Restricted to Those Randomized to Either Treatment Prior to the Closure of the Imiquimod Arm.
Complete response is defined as the absence of HSIL histology for all biopsies and the absence of HSIL cytology.
Compare the complete response by 5-FU vs Imiquimod across sites using stratified CMH test at one-sided 0.05 alpha using only the participants randomized to imiquimod and 5-FU prior to closure of the imiquimod arm.
Measured: Week 20
Percentage of Participants Achieving Complete Response in Imiquimod vs Observation Arm, Using ITT Population Restricted to Those Randomized to Either Treatment Prior to the Closure of the Imiquimod Arm.
Complete response is defined as the absence of HSIL histology for all biopsies and the absence of HSIL cytology.
Compare the complete response by Observation vs Imiquimod across sites using stratified CMH test at two-sided 0.05 alpha using only the participants randomized to imiquimod and observation prior to closure of the imiquimod arm.
Measured: Week 20
Percentage of Participants Achieving Complete Response in Imiquimod vs Observation Arm, Using Per Protocol Population Restricted to Those Randomized to Either Treatment Prior to the Closure of the Imiquimod Arm.
Complete response is defined as the absence of HSIL histology for all biopsies and the absence of HSIL cytology.
Compare the complete response by Observation vs Imiquimod across sites using stratified CMH test at two-sided 0.05 alpha using only the participants randomized to imiquimod and observation prior to closure of the imiquimod arm.
Measured: Week 20
Number of Participants With Peri-anal HSIL Confirmed by Histology Across All Study Arms
Perianal HSIL are HSIL lesions detected in peri-anal region; These lesions will be detected by visual inspection using high resolution anoscopy and biopsy.
Number of participants with presence of peri-anal HSIL on histology
Measured: At week 20
Number of Participants With Intra-anal HSIL
Intra-anal HSIL lesions are those lesions that are detected in intra-anal region. It will be detected using visual inspection using HRA followed by positive identification of HSIL using biopsy or cytology.
Presence of intra-anal HSIL lesions will be descriptively reported across the three arms
Measured: At week 20
Secondary outcomes (9)
Number of Participants Who Experienced an Adverse Event of Grade 1 to 5 by Week 44, Irrespective of Relatedness to the Intervention. AEs Were Stratified According to Those Reported at or Before Week 20 and After Week 20.
Adverse events are graded on a scale from 1 (mild) to 5 (death) as per CTCAE v. 5.0, with higher grades indicating greater severity.
The number of participants who experienced an adverse event of grade 1 to 5 by Week 44, regardless of its relatedness to the intervention, will be reported.
AEs were stratified according to those reported at or before Week 20 and after Week 20.
Measured: Up to week 44
Percentage of Participants Achieving Complete or Partial Response in 5-FU vs Observation Using ITT Population
Complete response is defined as the absence of HSIL histology for all biopsies and the absence of HSIL cytology.
Partial response is defined as either 1) The regression of HSIL histology but HSIL cytology is present, or 2) Reduction in number of octants with HSIL.
Percentages will be compared across sites using the stratified Mantel-Haenszel-Cochran test at the two-sided 0.05 alpha level.
Measured: Up to week 20
Percentageof Patients Achieving Complete or Partial Response in Imiquimod vs Observation Arm, Using ITT Population Restricted to Those Randomized to Either Treatment Prior to the Closure of the Imiquimod Arm.
Complete response is defined as the absence of HSIL histology for all biopsies and the absence of HSIL cytology. Partial response is defined as 1) The regression of HSIL histology but HSIL cytology is present, or 2) Reduction in number of octants with HSIL.
Percentage of patients achieving complete or partial responses with imiquimod will be compared to observation using participants randomized to imiquimod and observation prior to closure of the imiquimod arm.
Measured: Up to week 20
Amount of Drug Consumed in 5-FU and Imiquimod Arm by Week 16
Amount of study drug consumed by measuring the mass of study drug dispensed (weight of study drug container at baseline - weight of study drug at the end of treatment) by study arm (5FU vs imiquimod) by the time of receiving 8 cycle treatment
Measured: Week 16
Percentage of Participants Achieving Complete or Partial Response in 5-FU vs Observation Using ITT Population
Complete response is defined as the Complete response is defined as the absence of HSIL histology for all biopsies and the absence of HSIL cytology. Partial response is defined as 1) The regression of HSIL histology but HSIL cytology is present, or 2) Reduction in number of octants with HSIL.
Percentage will be compared across sites using the stratified Mantel-Haenszel-Cochran test at the two-sided 0.05 alpha level.
Measured: At 44 weeks
Percentage of Patients Achieving Complete or Partial Response in Imiquimod vs Observation Arm, Using ITT Population Restricted to Those Randomized to Either Treatment Prior to the Closure of the Imiquimod Arm.
The proportion of patients achieving complete or partial responses with imiquimod will be compared to observation using participants randomized to imiquimod and observation prior to closure of the imiquimod arm. Complete response is defined as the absence of HSIL based on central pathology review, if available; otherwise, local biopsy results will be used. Partial Response is defined as: 1) The regression of HSIL histology but HSIL cytology is present, or 2) Reduction in number of octants with HSIL.
Measured: Up to week 44
Persistence and New Infections of HPV Type Specific Infections
The proportion of participants with persistent HPV infection, defined as the presence of the same HPV type detected at both baseline and Week 20. The proportion of participants who acquire a new HPV infection at Week 20 that was not detected at baseline is new infection. Persistence and new infection will be assessed separately for each HPV type.
Measured: At week 20
Comparison of the Number of hrHPV Genotypes in Each Arm Observed at Baseline vs at Week 20
hrHPV genotypes will be detected in anal swabs specimens processed using polymerase chain reaction (PCR) and reverse line blot analysis.
Comparison of mean number of hrHPV genotypes in each arm observed at baseline vs at week 20
Measured: week 20
HPV Genotypes Present at Baseline But no Longer Detected at Week 20
Count of HPV genotypes present at baseline but no longer detected at week 20.
Measured: 20 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2014 (estimated)
- Study start28 Dec 2015
- Primary completion5 Dec 2023
- Study completion2 May 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Anal Intraepithelial NeoplasiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 91 participants (actual)
Sponsor and investigators
- Lead sponsor
- AIDS Malignancy Consortium
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI), The Emmes Company, LLC, University of Arkansas
- Responsible party
- Sponsor
- Investigators
- Timothy Wilkin, Principal investigator, AIDS Associated Malignancies Clinical Trials Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02059499
- Sponsor's protocol ID
- AMC-088
- Other IDs
- NCI-2013-02288, AMC-088, AMC-088, U01CA121947
- Status last verified
- Jul 2025
- First submitted
- 7 Feb 2014
- Last updated
- 23 Jul 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
Pedersen TB, Pachler FR, Rosenberg J, Andresen K. Interventions for anal canal intraepithelial neoplasia. Cochrane Database Syst Rev. 2025 Aug 13;8(8):CD009244. doi: 10.1002/14651858.CD009244.pub3.
PubMed 40801169
Study at a glance
From the registry record, last updated by the sponsor on 23 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT02059499
- Acronym / sponsor ID
- AMC-088
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 91 participants (actual)
- Lead sponsor
- AIDS Malignancy ConsortiumResearch network
- Collaborators
- National Cancer Institute (NCI), The Emmes Company, LLC, University of Arkansas
- Study start
- 28 Dec 2015 (actual)
- Primary completion
- 5 Dec 2023 (actual)
- Study completion
- 2 May 2024 (actual)
- First posted
- 11 Feb 2014 (estimated)
- Results
- Posted 20 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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.
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm A (imiquimod) | Experimental | Drug: imiquimod, Other: questionnaire administration, Other: laboratory biomarker analysisPatients apply imiquimod intra-anally QD for 16 weeks. |
| Arm B (fluorouracil) | Experimental | Drug: fluorouracil, Other: questionnaire administration, Other: laboratory biomarker analysisPatients 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. |
| Arm C (observation) | No intervention | –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. |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (11 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| imiquimodAlso: Aldara, IMQ, R 837Given intra-anally | Drug | Arm A (imiquimod) |
| fluorouracilAlso: 5-fluorouracil, 5-Fluracil, 5-FUGiven intra-anally | Drug | Arm B (fluorouracil) |
| questionnaire administrationAncillary studies | Other | Arm A (imiquimod), Arm B (fluorouracil) |
| laboratory biomarker analysisCorrelative studies | Other | Arm A (imiquimod), Arm B (fluorouracil) |
Primary outcome
Percentage of Participants Achieving Complete Response in 5-FU Arm and Observation Arm Using ITT Population
Time frame: At week 20
Complete response is defined as the absence of HSIL histology for all biopsies and the absence of HSIL cytology. The percentage of participants achieving complete response in the 5-FU and observation arms will be reported and compared across sites, along with the corresponding p-value, using stratified Mantel-Haenszel-Cochran tests at a one-sided alpha level of 0.025.
Percentage of Participants Achieving Complete Response (5-FU vs Observation ) Using Per Protocol Population
Time frame: At week 20
Complete response is defined as the absence of HSIL histology for all biopsies and the absence of HSIL cytology. The percentage of participants achieving complete response in the 5-FU and observation arms will be reported, along with the corresponding p-value, using stratified Mantel-Haenszel-Cochran tests to compare results across sites at a one-sided alpha level of 0.025.
Percentage of Participants Achieving Complete Response in 5-FU vs. Imiquimod, Using the ITT Population Restricted to Those Randomized to Either Treatment Prior to the Closure of the Imiquimod Arm.
Time frame: Week 20
Complete response is defined as an absence of HSIL histology for all biopsies and the absence of HSIL cytology. Compare the percentage of complete response in 5-FU vs Imiquimod arms across sites using stratified CMH test at one-sided 0.05 alpha.
Percentage of Participants Achieving Complete Response in 5-FU vs. Imiquimod, Using the PP Population Restricted to Those Randomized to Either Treatment Prior to the Closure of the Imiquimod Arm.
Time frame: Week 20
Complete response is defined as the absence of HSIL histology for all biopsies and the absence of HSIL cytology. Compare the complete response by 5-FU vs Imiquimod across sites using stratified CMH test at one-sided 0.05 alpha using only the participants randomized to imiquimod and 5-FU prior to closure of the imiquimod arm.
Percentage of Participants Achieving Complete Response in Imiquimod vs Observation Arm, Using ITT Population Restricted to Those Randomized to Either Treatment Prior to the Closure of the Imiquimod Arm.
Time frame: Week 20
Complete response is defined as the absence of HSIL histology for all biopsies and the absence of HSIL cytology. Compare the complete response by Observation vs Imiquimod across sites using stratified CMH test at two-sided 0.05 alpha using only the participants randomized to imiquimod and observation prior to closure of the imiquimod arm.
Percentage of Participants Achieving Complete Response in Imiquimod vs Observation Arm, Using Per Protocol Population Restricted to Those Randomized to Either Treatment Prior to the Closure of the Imiquimod Arm.
Time frame: Week 20
Complete response is defined as the absence of HSIL histology for all biopsies and the absence of HSIL cytology. Compare the complete response by Observation vs Imiquimod across sites using stratified CMH test at two-sided 0.05 alpha using only the participants randomized to imiquimod and observation prior to closure of the imiquimod arm.
Number of Participants With Peri-anal HSIL Confirmed by Histology Across All Study Arms
Time frame: At week 20
Perianal HSIL are HSIL lesions detected in peri-anal region; These lesions will be detected by visual inspection using high resolution anoscopy and biopsy. Number of participants with presence of peri-anal HSIL on histology
Number of Participants With Intra-anal HSIL
Time frame: At week 20
Intra-anal HSIL lesions are those lesions that are detected in intra-anal region. It will be detected using visual inspection using HRA followed by positive identification of HSIL using biopsy or cytology. Presence of intra-anal HSIL lesions will be descriptively reported across the three arms
9 secondary outcomes
Number of Participants Who Experienced an Adverse Event of Grade 1 to 5 by Week 44, Irrespective of Relatedness to the Intervention. AEs Were Stratified According to Those Reported at or Before Week 20 and After Week 20.
Time frame: Up to week 44
Percentage of Participants Achieving Complete or Partial Response in 5-FU vs Observation Using ITT Population
Time frame: Up to week 20
Percentageof Patients Achieving Complete or Partial Response in Imiquimod vs Observation Arm, Using ITT Population Restricted to Those Randomized to Either Treatment Prior to the Closure of the Imiquimod Arm.
Time frame: Up to week 20
Amount of Drug Consumed in 5-FU and Imiquimod Arm by Week 16
Time frame: Week 16
Percentage of Participants Achieving Complete or Partial Response in 5-FU vs Observation Using ITT Population
Time frame: At 44 weeks
Percentage of Patients Achieving Complete or Partial Response in Imiquimod vs Observation Arm, Using ITT Population Restricted to Those Randomized to Either Treatment Prior to the Closure of the Imiquimod Arm.
Time frame: Up to week 44
Persistence and New Infections of HPV Type Specific Infections
Time frame: At week 20
Comparison of the Number of hrHPV Genotypes in Each Arm Observed at Baseline vs at Week 20
Time frame: week 20
HPV Genotypes Present at Baseline But no Longer Detected at Week 20
Time frame: 20 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40801169Pedersen TB, Pachler FR, Rosenberg J, Andresen K. Interventions for anal canal intraepithelial neoplasia. Cochrane Database Syst Rev. 2025 Aug 13;8(8):CD009244. doi: 10.1002/14651858.CD009244.pub3.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Timothy Wilkin principal investigator
AIDS Associated Malignancies Clinical Trials Consortium
13 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing imiquimod, fluorouracil and questionnaire administration in people with Anal Intraepithelial Neoplasia and High-grade Squamous Intraepithelial Lesion, run by AIDS Malignancy Consortium at 13 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants Achieving Complete Response in 5-FU Arm and Observation Arm Using ITT Population (time frame: At week 20). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02059499, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jul 2025.