Acceptability and Feasibility of Combination Treatment for Cervical Precancer Among South African Women Living With HIV

Study Overview
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Brief Summary
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The purpose of this study is to explore whether an anti-cancer medication (5-fluorouracil cream) placed in the vagina after a surgical excision procedure is an acceptable and useful form of treatment for cervical precancer among the woman with HIV infection.

Detailed Description
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There are currently no medical therapies recommended to promote the clearance of humanpapilloma virus (HPV) infection, regression of cervical dysplasia, or treatment of cervical intraepithelial neoplasia (CIN). Human immunodeficiency virus (HIV) -infected women are at higher risk of HPV infection, with rates as high as 45% - 90%. Despite being preventable, cytologic abnormalities, cervical precancer (high-grade cervical intraepithelial neoplasia [CIN2/3]), and invasive cervical cancer also occur more frequently in HIV infected women. This study is testing whether topical 5-fluorouracil (5FU) can be used as a patient-controlled adjuvant treatment for cervical precancer (CIN2/3) to be self-administered after surgical excision to reduce the risk of persistent/recurrent CIN2/3 and progression to cervical cancer among HIV-infected women.

Official Title
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Acceptability and Feasibility of Combination Treatment for Cervical Precancer Among South African Women Living With HIV

Conditions
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Cervical Cancer, CIN2, CIN3, Human Immunodeficiency Virus, Human Papillomavirus

Intervention / Treatment
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* Drug: 5 Fluorouracil (5 FU) Cream
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed HIV-1 infection On antiretroviral therapy (ART), for at least 90 days prior to enrollment Cervical biopsy demonstrating CIN2/3 within the preceding 120 days. Exclusion Criteria: pregnancy, breastfeeding, intend to become pregnant within 180 days of enrollment have an active sexually transmitted infection (women may participate once treated) have a surgically absent cervix have a history of anogenital (cervical, vaginal, vulvar, or anal) cancer or a biopsy suspicious for cervical cancer have a medical comorbidity that would interfere with study participation.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 5 Fluorouracil Cream<br>The participants will receive 8 doses of intravaginal 5 Fluorouracil Cream. | Drug: 5 Fluorouracil (5 FU) Cream<br>* Intravaginal topical chemotherapy, 5-fluorouracil cream<br>* Other names: Carac;|
| Placebo Comparator: Placebo Cream<br>The participants will receive 8 doses of intravaginal placebo cream. | Drug: Placebo<br>* Intravaginal topical placebo cream<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of subjects adhered to and retained in the study | The feasibility of the combination of surgical excision followed by adjuvant 5FU for the treatment of CIN2/3 among HIV-infected women will be evaluated using the number of subjects adhered to and retained in the study. | Up to 24 weeks | 
| The number of participants who found the intervention acceptable | The acceptability of the combination of surgical excision followed by adjuvant 5FU for the treatment of CIN2/3 among HIV-infected women will be assessed through a participant questionnaire administered at midline and end of the study. | week 10 to week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of participants with CIN2 or CIN 3 that regressed to CIN1 | Efficacy of combination treatment for CIN2/3 will be assessed as the number of subjects with CIN2 or CIN3 regressed to CIN1 or normal histology. | 24 weeks | 
| The percentage of participants who demonstrate clearance of high-risk HPV | Efficacy of combination treatment for HPV will be assessed as the percentage of women in each study arm who demonstrate clearance of high-risk HPV between baseline and 24 weeks. | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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5-fluorouracil cream, Loop electrosurgical excision