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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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)

Conditions
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Vulvar Dysplasia, HPV-Related Vulvar Intraepithelial Neoplasia, Preinvasive Vulvar Disease, Vulva Intraepithelial Neoplasia, Vulvar Diseases

Intervention / Treatment
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* Drug: artesunate ointment 40%


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Artesunate ointment 40%, 1 cycle<br>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%<br>* artesunate formulated as an ointment to be applied topically to the vulva<br>|
| Experimental: Artesunate ointment 40%, 2 cycles<br>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%<br>* artesunate formulated as an ointment to be applied topically to the vulva<br>|
| Experimental: Artesunate ointment 40%, 3 cycles<br>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%<br>* artesunate formulated as an ointment to be applied topically to the vulva<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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 | 15 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of artesunate ointment as assessed by number of participants with regression to VIN1 or less at week 15 | 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. | 15 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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artesunate, pre-invasive disease, treatment, alternative, non-surgical, cancer prevention