Adjuvant 5-Fluorouracil Following Thermal Ablation to Improve HPV Treatment Outcomes in Women With HIV in Kenya (ASCEND)

UNC Lineberger Comprehensive Cancer Center

Status and phase: Begins enrollment this month; Phase 2

Conditions: CIN; CIN1; HPV Infection; Cervical Intraepithelial Neoplasia Grade 3; CIN2; CIN3; Cervical Intraepithelial Neoplasia Grade 1; HIV Infections; Cervical Intraepithelial Neoplasia Grade 2/3; Cervix Cancer

Treatments: Drug: Placebo Cream; Drug: 5% 5-fluorouracil Topical Cream

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT07545746

LCCC2531

3R37CA306827-01S2 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

This randomized, placebo-controlled trial will evaluate self-administered 5-fluorouracil (5FU) to improve human papillomavirus (HPV) clearance after thermal ablation (TA) in Women With Human Immunodeficiency Virus (HIV) (WWH) in Kenya. The trial will also assess the safety, adherence, and acceptability of 5FU. Starting four weeks after TA, participants will self-administer 5FU cream or matched placebo intravaginally once every other week for 12 applications, with clinic visits at weeks 2, 8, 16, 24, and 48 for evaluation. All participants will be followed up to 48 weeks.

It is hypothesized that, compared to placebo, 5FU will increase HPV clearance at 24 weeks and that the proposed dosing schedule will be safe, well-tolerated, and acceptable in this population. Together with data from other studies, this trial will provide evidence on the use of self-administered intravaginal 5FU to improve HPV treatment outcomes in WWH in low- and middle-income countries, where the burden of cervical cancer is highest.

Full description

WWH face up to six times higher risk of cervical cancer, a leading cause of death in this population. Cervical cancer is caused by persistent HPV infection, which can lead to cervical intraepithelial neoplasia grade 2/3 (CIN2/3), also called cervical precancer. If untreated, CIN2/3 can progress to cervical cancer. Thermal ablation (TA) is the most commonly used treatment for HPV/precancer in low- and middle-income countries, including Kenya. However, among WWH, TA has suboptimal efficacy, with only 44-66% clearing HPV or CIN2/3 at 6-12 months, compared to 83-95% in women without HIV. This highlights the need for adjuvant therapies to improve outcomes.

Studies in high-income countries suggest that off-label, self-administered intravaginal 5FU cream can improve HPV and CIN2/3 treatment outcomes in both HIV-negative and HIV-positive women. This trial will evaluate its potential as an adjuvant therapy following TA in WWH.

Enrollment: 140 estimated patients

Sex: Female

Ages: 25+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

• Women aged 25 years or older
• Known HIV-positive status
• On antiretroviral therapy (ART) for at least 60 days prior to enrollment
• Positive HPV screening test screening result
• Able to provide informed consent in English, Swahili, or Dholuo
• Agree to use dual contraception during dosing phase if of childbearing potential
• Planning to remain in study locale for duration of study (48 weeks) Exclusion Criteria
• Current pregnancy or breastfeeding
• History of anogenital cancer (cervical, vulvar, or anal)
• Current use of immunosuppressive medications
• History of total hysterectomy
• Known allergy to 5FU
• Medical comorbidity that would interfere with study participation
• Unwilling or unable to use contraception during study participation

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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140 participants in 2 patient groups, including a placebo group

5% 5-fluorouracil

Experimental group

Description:

Participants will receive 12 doses of intravaginal 5FU cream.

Treatment:

Drug: 5% 5-fluorouracil Topical Cream

Placebo cream

Placebo Comparator group

Description:

Participants will receive 12 doses of intravaginal placebo cream.

Treatment:

Drug: Placebo Cream