ACT2: Acceptability and Feasibility of Combination Treatment for Cervical Precancer Among South African Women Living With HIV

Sponsor

UNC Lineberger Comprehensive Cancer Center (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05413811

Collaborator

National Cancer Institute (NCI) (NIH)

180

Enrollment

Location

Arms

Anticipated Duration (Months)

5.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Cervical Cancer CIN2 CIN3 Human Immunodeficiency Virus Human Papillomavirus	Drug: 5 Fluorouracil (5 FU) Cream Drug: Placebo	N/A

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

180 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

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

Anticipated Study Start Date :

Oct 1, 2022

Anticipated Primary Completion Date :

May 31, 2025

Anticipated Study Completion Date :

May 31, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 5 Fluorouracil Cream The participants will receive 8 doses of intravaginal 5 Fluorouracil Cream.	Drug: 5 Fluorouracil (5 FU) Cream Intravaginal topical chemotherapy, 5-fluorouracil cream Other Names: Fluoroplex Efudex Carac
Placebo Comparator: Placebo Cream The participants will receive 8 doses of intravaginal placebo cream.	Drug: Placebo Intravaginal topical placebo cream

Arm

Intervention/Treatment

Experimental: 5 Fluorouracil Cream

The participants will receive 8 doses of intravaginal 5 Fluorouracil Cream.

Drug: 5 Fluorouracil (5 FU) Cream

Intravaginal topical chemotherapy, 5-fluorouracil cream

Other Names:

Fluoroplex

Efudex

Carac

Placebo Comparator: Placebo Cream

The participants will receive 8 doses of intravaginal placebo cream.

Drug: Placebo

Intravaginal topical placebo cream

Outcome Measures

Primary Outcome Measures

The number of subjects adhered to and retained in the study [Up to 24 weeks]
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.
The number of participants who found the intervention acceptable [week 10 to week 24]
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.

Secondary Outcome Measures

The proportion of participants with CIN2 or CIN 3 that regressed to CIN1 [24 weeks]
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.
The percentage of participants who demonstrate clearance of high-risk HPV [24 weeks]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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.