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

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.

Study Overview

• Status: Recruiting
• Conditions: Cervical Cancer; Human Immunodeficiency Virus; Human Papillomavirus; CIN2; CIN3
• Intervention / Treatment: Drug: 5 Fluorouracil (5 FU) Cream; Drug: Placebo

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 Type: Interventional
• Enrollment (Estimated): 180
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Cheryl Hendrickson; Phone Number: +1 (919) 843-2541; Email: cheryl_hendrickson@med.unc.edu

Study Locations

• South Africa
  • Johannesburg
    • Westdene, Johannesburg, South Africa, 2092
      • Recruiting
      • Clinical HIV Research Unit Temba Lethu Wing Helen Joseph Hospital
      • Principal Investigator: Carla Chibwesha, MD, MSc
      • Contact: Sibusisiwe Luvuno; Email: sluvuno@witshealth.co.za

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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: Carac; Efudex; Fluoroplex
Placebo Comparator: Placebo Cream; The participants will receive 8 doses of intravaginal placebo cream.	Drug: Placebo; Intravaginal topical placebo cream

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: UNC Lineberger Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Carla Chibwesha, MD, MSc, University of North Carolina, Chapel Hill

Publications and helpful links

Helpful Links

• University of North Carolina Lineberger Comprehensive Cancer Center Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2023
• Primary Completion (Estimated): May 31, 2025
• Study Completion (Estimated): May 31, 2025

Study Registration Dates

• First Submitted: June 7, 2022
• First Submitted That Met QC Criteria: June 7, 2022
• First Posted (Actual): June 10, 2022

Study Record Updates

• Last Update Posted (Estimated): February 2, 2024
• Last Update Submitted That Met QC Criteria: February 1, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: 5-fluorouracil cream; Loop electrosurgical excision
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Precancerous Conditions; Slow Virus Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; HIV Infections; Acquired Immunodeficiency Syndrome; Uterine Cervical Dysplasia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Fluorouracil
• Other Study ID Numbers: IGHID12046; 1R01CA250850-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The rights and privacy of individuals who participate in research will be protected at all times. Thus, data intended for broader use will be stripped of identifiers that would permit linkages to individual research participants or variables that could lead to deductive disclosure of the identity of individual subjects. Research data that documents, supports and validates research findings will be made available after the main findings from the final research dataset have been accepted for publication. Such research data will be redacted to prevent the disclosure of personal identifiers. All data sharing will abide by rules and/or policies defined by the sponsor, relevant IRBs, U.S. local, state, and federal laws and regulations, as well as South African laws and regulations.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No