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

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).

Study Overview

• Status: Completed
• Conditions: HIV Infections; CIN 2/3
• Intervention / Treatment: Drug: Intravaginal 5-Fluorouracil (5-FU)

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Kenya
  • Kisumu, Kenya, 614-40100
    • Lumumba Sub-County Hospital KEMRI- Research Care Training Program (RCTP) Building

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 49 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Subjects must meet all of the inclusion criteria to participate in this study.

Inclusion Criteria:

1. HIV-positive women
2. Age 18 years - 49 years at enrollment
3. Documentation of a biopsy-confirmed CIN2 or CIN3
4. Within 4-12 weeks after primary treatment for CIN2 or CIN3
5. 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.
6. Agree to use dual contraception if of childbearing age (hormonal method, intrauterine or implant device, or tubal ligation - plus condoms) for duration of study
7. Ability to understand and willingness to sign (or assent when applicable) informed consent

Exclusion Criteria:

1. HIV-negative women
2. Pregnant or planning pregnancy within the next 6 months or breastfeeding
3. Unwilling or unable to use birth control during participation in the study
4. History of invasive cervical cancer
5. Untreated vaginal or vulvar dysplasia
6. Known allergy to 5-Fluorouracil
7. History of total hysterectomy
8. Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient
9. Current use of chemotherapeutic medication or high dose steroids (10 mg prednisone per day or more (or equivalent steroids)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 5-FU Arm; intravaginal 2g 5-fluorouracil cream in every two weeks	Drug: Intravaginal 5-Fluorouracil (5-FU); 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: UNC Lineberger Comprehensive Cancer Center
• Investigators: Principal Investigator: Chemtai Mungo, MD, MPH, Assistant Professor, Obstetrics and Gynecology

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): April 26, 2023
• Primary Completion (Actual): February 1, 2024
• Study Completion (Actual): February 1, 2024

Study Registration Dates

• First Submitted: May 2, 2022
• First Submitted That Met QC Criteria: May 2, 2022
• First Posted (Actual): May 5, 2022

Study Record Updates

• Last Update Posted (Actual): August 23, 2024
• Last Update Submitted That Met QC Criteria: August 21, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: cervical cancer; 5-Fluorouracil; CIN 2/3
• Additional Relevant MeSH Terms: Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Precancerous Conditions; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; 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: UNCPM22120

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No