5-fluorouracil Following Cervical Intraepithelial Neoplasia Treatment Among HIV-positive Women in East Africa

Study Overview
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Brief Summary
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This is a single arm study on the safety, feasibility, and acceptability of adjuvant, self-administered, intravaginal 5-Fluorouracil (5-FU) following treatment for high-grade cervical precancer (CIN2/3) among women living with human immunodeficiency virus (HIV).

Official Title
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5-fluorouracil Following Cervical Intraepithelial Neoplasia Treatment Among HIV-positive Women in East Africa

Conditions
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CIN 2/3, HIV Infections

Intervention / Treatment
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* Drug: Intravaginal 5-Fluorouracil (5-FU)


Participation Criteria
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Eligibility Criteria
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Subjects must meet all of the inclusion criteria to participate in this study. Inclusion Criteria: HIV-positive women Age 18 years - 49 years at enrollment Documentation of a biopsy-confirmed CIN2 or CIN3 Within 4-12 weeks after primary treatment for CIN2 or CIN3 Negative pregnancy test at screening and agreement to use dual form of contraception (hormonal birth control, intrauterine device, or tubal ligation - plus condoms) during the study duration, if of childbearing age. Agree to use dual contraception if of childbearing age (hormonal method, intrauterine or implant device, or tubal ligation - plus condoms) for duration of study Ability to understand and willingness to sign (or assent when applicable) informed consent Exclusion Criteria: HIV-negative women Pregnant or planning pregnancy within the next 6 months or breastfeeding Unwilling or unable to use birth control during participation in the study History of invasive cervical cancer Untreated vaginal or vulvar dysplasia Known allergy to 5-Fluorouracil History of total hysterectomy Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient Current use of chemotherapeutic medication or high dose steroids (10 mg prednisone per day or more (or equivalent steroids)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 5-FU Arm<br>intravaginal 2g 5-fluorouracil cream in every two weeks | Drug: Intravaginal 5-Fluorouracil (5-FU)<br>* Participants will self-administer 2 g of 5% 5-FU intravaginally using an applicator, one night per week (every other week), on weeks 1, 3, 5, 7, 9, 11, 13, 15, for a total of 8 applications.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of intravaginal 5-FU | Safety will be evaluated as type, frequency, and severity of Adverse Events (AE)s. AEs will be evaluated according to the National Institute of Health (NIH) Division of Acquired Immunodeficiency Syndrome (DAIDS) Adverse Event Grading Tables. The DAIDS grading table provides an AE severity grading scale ranging from grades 1 to 5. 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 and Grade 5 indicates death. | Up to 5 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerability of intravaginal 5-FU | Tolerability will be evaluated by assessing the number of participants experiencing specified adverse events (SAEs), defined as a Grade 3 or 4 toxicity that is possibly, probably, or definitely related to the study agent. | Up to 5 months | 
| Adherence of intravaginal 5-FU | Adherence will be evaluated by assessing the number of participants who are confirmed to use 75% or more of the 5-FU applications. | Up to 5 months | 
| Acceptability of intravaginal 5-FU | Responses to an acceptability questionnaire will be summarized, including means and standard deviation for responses to questions graded on a Likert scale (from 0 to 4), and proportions and 95% confidence intervals for yes/no questions. | Up to 20 weeks | 
| Uptake of intravaginal 5-FU | The proportion of eligible screened participants who agree to participate in the trial and applied intravaginal 5-FU as the study defined. | Up to 20 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cervical cancer, CIN 2/3, 5-Fluorouracil