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

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)

Overall Status

Recruiting

CT.gov ID

NCT03792516

Collaborator

Frantz Viral Therapeutics, LLC (Industry)

Enrollment

Locations

Arms

42.5

Anticipated Duration (Months)

3.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Vulvar Dysplasia HPV-Related Vulvar Intraepithelial Neoplasia Preinvasive Vulvar Disease Vulva Intraepithelial Neoplasia Vulvar Diseases	Drug: artesunate ointment 40%	Phase 1

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 Design

Study Type:

Interventional

Anticipated Enrollment :

15 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I Proof-of-Concept Study of Artesunate Ointment for the Treatment of Patients With High-Grade Vulvar Intraepithelial Neoplasia (HSIL VIN 2/3)

Actual Study Start Date :

Apr 17, 2019

Anticipated Primary Completion Date :

Jul 31, 2022

Anticipated Study Completion Date :

Oct 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Artesunate ointment 40%, 1 cycle Patients enrolled in this treatment group will receive one 5-day cycle of artesunate ointment applied topically to the vulva at week 0.	Drug: artesunate ointment 40% artesunate formulated as an ointment to be applied topically to the vulva
Experimental: Artesunate ointment 40%, 2 cycles 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.	Drug: artesunate ointment 40% artesunate formulated as an ointment to be applied topically to the vulva
Experimental: Artesunate ointment 40%, 3 cycles 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.	Drug: artesunate ointment 40% artesunate formulated as an ointment to be applied topically to the vulva

Arm

Intervention/Treatment

Experimental: Artesunate ointment 40%, 1 cycle

Patients enrolled in this treatment group will receive one 5-day cycle of artesunate ointment applied topically to the vulva at week 0.

Drug: artesunate ointment 40%

artesunate formulated as an ointment to be applied topically to the vulva

Experimental: Artesunate ointment 40%, 2 cycles

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.

Drug: artesunate ointment 40%

artesunate formulated as an ointment to be applied topically to the vulva

Experimental: Artesunate ointment 40%, 3 cycles

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.

Drug: artesunate ointment 40%

artesunate formulated as an ointment to be applied topically to the vulva

Outcome Measures

Primary Outcome Measures

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

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 100 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Johns Hopkins Outpatient Center	Baltimore	Maryland	United States	21205
2	Cleveland Clinic Fairview Hospital	Cleveland	Ohio	United States	44111
3	Cleveland Clinic Foundation - Main Campus	Cleveland	Ohio	United States	44195
4	Cleveland Clinic - Hillcrest Hospital	Mayfield Heights	Ohio	United States	44124