Imiquimod vs. Fluorouracil for Anal Lesions in HIV/AIDS

No longer recruiting at 13 trial locations
LF
Overseen ByLisa Flowers, MD
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Pivotal Trial (Near Approval)This treatment is in the last trial phase before FDA approval
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments, imiquimod and fluorouracil, to evaluate their effectiveness compared to no treatment for high-grade anal lesions in HIV-positive individuals. Imiquimod boosts the immune system to fight tumor cells, while fluorouracil, a chemotherapy drug, stops tumor cells from growing. The trial seeks HIV-positive individuals diagnosed with high-grade squamous lesions in the anal area. Participants should be able to apply the treatment themselves and must not have a history of anal cancer. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are using anticoagulants (except aspirin or NSAIDs) or certain immune system therapies. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that both imiquimod and fluorouracil are generally safe for treating anal lesions in people with HIV. Studies have found that imiquimod is a safe option for treating anal high-grade squamous intraepithelial lesions (HSIL), especially in HIV-positive men. It boosts the immune system to help fight off abnormal cells.

Fluorouracil, a type of chemotherapy, helps stop the growth of tumor cells. Research has shown that many HIV-positive men with anal lesions experienced lesion clearance after using fluorouracil.

Previous studies indicate that both treatments have been well-tolerated, with most patients not experiencing severe side effects. However, some individuals might experience mild skin irritation where the cream is applied. This evidence suggests that these treatments are relatively safe options for those with anal lesions and HIV.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for anal lesions in HIV/AIDS patients because they offer unique approaches compared to traditional options. Imiquimod stands out by leveraging the immune system to fight off lesions, as it is an immune response modifier applied directly to the affected area. On the other hand, Fluorouracil acts as a topical chemotherapy agent, disrupting the DNA of abnormal cells to prevent their growth. Unlike more invasive procedures like surgery, these topical treatments could provide less painful and more convenient alternatives for patients, with potential for fewer side effects.

What evidence suggests that this trial's treatments could be effective for high-grade anal squamous skin lesions in HIV-positive patients?

This trial will compare the effectiveness of Imiquimod and Fluorouracil for treating anal intraepithelial neoplasia (AIN) in people with HIV. Studies have shown that Imiquimod, which participants in this trial may receive, can be effective, with 45% of patients showing complete or partial improvement. Imiquimod boosts the immune system to fight abnormal cells. Meanwhile, Fluorouracil, another treatment option in this trial, has cleared lesions in many HIV-positive patients; specifically, more than half of the patients in one study had their lesions cleared. Both treatments show promise in reducing the risk of high-grade lesions developing into anal cancer.12346

Who Is on the Research Team?

TW

Timothy Wilkin

Principal Investigator

AIDS Associated Malignancies Clinical Trials Consortium

Are You a Good Fit for This Trial?

This trial is for HIV-positive patients with high-grade anal squamous skin lesions. They must have a Karnofsky performance status of >= 70%, CD4 count >= 200 or low viral load, and visible HSIL occupying at least 25% of the anal canal circumference. Exclusions include history of anal cancer, recent use of certain treatments like fluorouracil or imiquimod, ongoing anticoagulant therapy other than aspirin/NSAIDs, acute infections, systemic corticosteroids or immunomodulatory therapy usage.

Inclusion Criteria

I am HIV-positive with documented test results or a doctor's diagnosis.
Platelet count >= 75,000/mm^3 within 90 days prior to enrollment
My recent biopsy showed high-grade anal lesions.
See 9 more

Exclusion Criteria

I have been vaccinated against HPV.
My cancer needs treatment that affects my whole body.
I am not currently taking steroids, cytokines, or immunomodulatory therapy.
See 8 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either imiquimod or fluorouracil treatment, or observation. Imiquimod is applied intra-anally once daily for 16 weeks, while fluorouracil is applied intra-anally twice daily on days 1-5, repeating every 2 weeks for 8 courses.

16 weeks
Regular visits as per treatment protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up visits at weeks 20, 24, 26, 32, 40, and 44.

24 weeks
6 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

  • Fluorouracil
  • Imiquimod
Trial Overview The effectiveness of biological therapy imiquimod versus chemotherapy drug fluorouracil is being tested against observation alone in treating high-grade anal squamous skin lesions in HIV-positive patients. The study aims to determine which method stops tumor growth more effectively.
How Is the Trial Designed?
3Treatment groups
Experimental Treatment
Active Control
Group I: Arm B (fluorouracil)Experimental Treatment3 Interventions
Group II: Arm A (imiquimod)Experimental Treatment3 Interventions
Group III: Arm C (observation)Active Control1 Intervention

Fluorouracil is already approved in United States, European Union, Canada for the following indications:

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Approved in United States as 5-Fluorouracil for:
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Approved in European Union as 5-Fluorouracil for:
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Approved in Canada as 5-Fluorouracil for:

Find a Clinic Near You

Who Is Running the Clinical Trial?

AIDS Malignancy Consortium

Lead Sponsor

Trials
64
Recruited
9,600+

The Emmes Company, LLC

Industry Sponsor

Trials
149
Recruited
1,052,000+
Peter Ronco profile image

Peter Ronco

The Emmes Company, LLC

Chief Executive Officer since 2023

BSc from Nottingham University

Dr. Joe Sliman profile image

Dr. Joe Sliman

The Emmes Company, LLC

Chief Medical Officer since 2020

MD from Uniformed Services University of the Health Sciences, MPH from Johns Hopkins University, BSc in Molecular and Cell Biology from Pennsylvania State University

University of Arkansas

Collaborator

Trials
500
Recruited
153,000+

National Cancer Institute (NCI)

Collaborator

Trials
14,080
Recruited
41,180,000+

Citations

1.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/20716208/
Topical 5-fluorouracil treatment of anal intraepithelial ...A substantial proportion of HIV-positive MSM with AIN completely cleared their lesions with topical 5-FU treatment.
Treatment of Anal High-Grade Squamous Intraepithelial ...The purpose of the Anal Cancer–HSIL Outcomes Research (ANCHOR) trial was to determine whether treating anal HSIL is effective and safe in ...
Imiquimod, Fluorouracil, or Observation in Treating HIV- ...This randomized phase III trial studies imiquimod or fluorouracil to see how well they work compared to observation in treating patients with high-grade ...
Initial Experience with Topical Fluorouracil for Treatment of ...We retrospectively reviewed records of the first 11 HIV-positive patients treated with topical 5-FU in our anal dysplasia clinic. Six (55%) ...
Topical 5‐fluorouracil treatment of anal intraepithelial ...Topical 5‐fluorouracil treatment of anal intraepithelial neoplasia in human immunodeficiency virus‐positive men. O. Richel,. O. Richel. Department of Internal ...
Imiquimod and 5% Fluorouracil Therapy for Anal ...A 59-year-old human immunodeficiency virus-1–positive (HIV-1+)white man presented with a nonhealing area that extended extensively aroundthe perianal skin.
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