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| ID | Type | Description | Link |
|---|---|---|---|
| 3R37CA306827-01S2 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
| UNC Department of Obstetrics and Gynecology | UNKNOWN |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 5% 5-fluorouracil | Experimental | Participants will receive 12 doses of intravaginal 5FU cream. |
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| Placebo cream | Placebo Comparator | Participants will receive 12 doses of intravaginal placebo cream. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 5% 5-fluorouracil Topical Cream | Drug | Starting four weeks after thermal ablation, participants will self-administer 2 g of 5FU cream intravaginally once every two weeks for 12 doses. |
| Measure | Description | Time Frame |
|---|---|---|
| High-risk human papillomavirus (hrHPV) Clearance among WWH randomized to adjuvant self-administered 5FU cream versus placebo cream following Thermal ablation (TA) | Vaginal samples will be collected at baseline and approximately every four weeks. Clearance of hrHPV genotypes will be assessed using Polymerase Chain Reaction (PCR)-based human papillomavirus (HPV) Deoxyribonucleic Acid (DNA) testing on these follow-up samples. | Up to 24 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Adverse Event per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 | Type, frequency, severity and duration of adverse events (AEs) using NCI CTCAE v5.0 will be reported. The NCI Common Terminology Criteria for Adverse Events is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE. |
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Inclusion Criteria
Women aged 25 or older in Western Kenya who have both HIV and human papillomavirus (HPV) infections.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Sorgi Kate | Contact | 919-984-0000 | kasorgi@email.unc.edu |
| Name | Affiliation | Role |
|---|---|---|
| Chemtai Mungo, MD, MPH | UNC Lineberger Comprehensive Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Maseno University | Kisumu | 614-40100 | Kenya |
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| Label | URL |
|---|---|
| University of North Carolina Lineberger Comprehensive Cancer Center Clinical Trials | View source |
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| Placebo Cream | Drug | Starting four weeks after thermal ablation, participants will self-administer 2g of placebo cream intravaginally once every two weeks for 12 doses. |
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| 24 weeks |
| Adverse Event per National Institute of Health (NIH) Division of Acquired Immunodeficiency Syndrome (AIDS) Adverse Event Grading Criteria (DAIDS) | Type, frequency, severity and duration of adverse events (AEs) using per DAIDS standardized scales will be reported. The DAIDS grading table provides an AE severity grading scale ranging from grades 1 to 5 with descriptions for each AE based on the following general guidelines: Grade 1 indicates a mild event, Grade 2 indicates a moderate event, Grade 3 indicates a severe event, Grade 4 indicates a potentially life-threatening event, Grade 5 indicates death. | Up to 24 weeks |
| Number of successful self-administration of the intravaginal cream by participants | Number of confirmed successful self-administrations of intravaginal 5FU or placebo cream by participants. | Up to 24 weeks |
| Nyanza Reproductive Health Society | Kisumu | Kenya |
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| ID | Term |
|---|---|
| D015658 | HIV Infections |
| D030361 | Papillomavirus Infections |
| D002583 | Uterine Cervical Neoplasms |
| D002578 | Uterine Cervical Dysplasia |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
| D004266 | DNA Virus Infections |
| D014412 | Tumor Virus Infections |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D014594 | Uterine Neoplasms |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D002577 | Uterine Cervical Diseases |
| D014591 | Uterine Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D011230 | Precancerous Conditions |
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