Artesunate Ointment for the Treatment of High Grade Vulvar Intraepithelial Neoplasia (HSIL VIN2/3)

Phase 1

Completed

• Conditions: Vulvar Diseases; HPV-Related Vulvar Intraepithelial Neoplasia; Vulvar Dysplasia; Vulva Intraepithelial Neoplasia; Preinvasive Vulvar Disease
• Interventions: Drug: artesunate ointment 40%

• Registration Number: NCT03792516
• Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief Summary

This is a Phase I, proof-of-concept treatment study to evaluate the safety, tolerability and feasibility of topical artesunate ointment to treat high grade vulvar intraepithelial neoplasia (HSIL VIN2/3).

Detailed Description

Phase I open-label dose escalation study of topical artesunate, formulated as ointment, in the treatment of adult females with biopsy-confirmed HSIL VIN2/3. Fifteen (15) subjects will undergo up to a total of three cycles of topical artesunate. The first cycle will be initiated on Day 0, the second at Week 2, and the third and final cycle at week 4.

Primary Objective:

To evaluate the safety and tolerability of artesunate ointment applied topically on VIN2/3 lesions

To measure the effect of artesunate ointment on histologic regression of HSIL/VIN2/3 to VIN1 or less, confirmed by a colposcopically-directed biopsy, at study week 15.

Study Timeline

• Study First Submitted: 2019-01-02
• Study First Submitted QC: 2019-01-02
• Study First Posted: 2019-01-03
• Study Start: 2019-04-17
• Primary Completion: 2022-08-31
• Status Verified: 2024-12
• Study Completion: 2024-12-03
• Last Update Submitted: 2024-12-03
• Last Update Posted: 2024-12-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 15

Inclusion Criteria

• Colposcopically-directed biopsy diagnosis of high-grade vulvar dysplasia (VIN2, VIN3, VIN2/3, HSIL), including both new and recurrent disease.
• Females of childbearing potential: negative urine pregnancy test
• Ability to provide informed consent
• Ability to collaborate with planned follow-up (transportation, compliance history, etc.)
• Use of contraception through the study exit visit (week 28)

Exclusion Criteria

• Concomitant use of any topical immune modulating agents e.g. imiquimod, Aldara ®
• Cluster of differentiation 4 (CD4) count < 200 at the time of screening for eligibility.
• Unable to provide informed consent
• Currently receiving systemic chemotherapy or radiation therapy for another cancer.
• Pregnant females
• Concurrent dermatological disorders involving the vulva (i.e., herpes, ulceration secondary to Crohn's disease) or vulvar dermatosis (i.e., lichen planus, lichen sclerosus, or lichen simplex chronicus);
• Women weighing less than 50 kg

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Artesunate ointment 40%, 1 cycle	artesunate ointment 40%	Patients enrolled in this treatment group will receive one 5-day cycle of artesunate ointment applied topically to the vulva at week 0.
Artesunate ointment 40%, 2 cycles	artesunate ointment 40%	Patients enrolled in this treatment group will receive two 5-day cycles of artesunate ointment applied topically to the vulva at weeks 0 and 2.
Artesunate ointment 40%, 3 cycles	artesunate ointment 40%	Patients enrolled in this treatment group will receive three 5-day cycles of artesunate ointment applied topically to the vulva at weeks 0, 2, and 4.

Primary Outcome Measures

Name	Time	Method
Safety and tolerability of artesunate ointment applied topically on VIN2/3 lesions as assessed by number of participants experiencing serious adverse events or dose-limiting toxicities	15 weeks	Number of participants with study-related serious adverse events or dose-limiting toxicities assessed using Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0) criteria

Secondary Outcome Measures

Name	Time	Method
Effect of artesunate ointment as assessed by number of participants with regression to VIN1 or less at week 15	15 weeks	Number of participants with histologic regression of HSIL/VIN2/3 to VIN1 or less on colposcopically-directed biopsy, at study week 15 after receiving artesunate ointment therapy.

Trial Locations

Locations (4)

Johns Hopkins Outpatient Center; 🇺🇸 Baltimore, Maryland, United States

Cleveland Clinic Fairview Hospital; 🇺🇸 Cleveland, Ohio, United States

Cleveland Clinic Foundation - Main Campus; 🇺🇸 Cleveland, Ohio, United States

Cleveland Clinic - Hillcrest Hospital; 🇺🇸 Mayfield Heights, Ohio, United States