A Study to Evaluate Once-Daily Oral VT-464 in Patients With Castration-Resistant Prostate Cancer

Study Overview
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Brief Summary
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The goal of this clinical study is to determine the safety, tolerability, pharmacokinetics and activity of once-daily (QD) oral dosing of VT-464, a lyase-selective inhibitor of CYP17, in patients with castration-resistant prostate cancer (CRPC).

Detailed Description
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This is a Phase 1/2 study of VT-464 in chemotherapy-naïve CRPC patients who are treatment-naive or who have failed prior therapy with abiraterone and/or enzalutamide. The study will examine several parallel QD dosing regimens of VT-464 using a traditional modified 3+3 Fibonacci study design. Approximately 3 dose-levels of VT-464 will be examined in each dosing regimen that is fully enrolled.

Official Title
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A Phase 1/2 Open-Label, Multiple-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Once-Daily VT-464 in Patients With Castration-Resistant Prostate Cancer

Conditions
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Castration-resistant Prostate Cancer, CRPC

Intervention / Treatment
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* Drug: VT-464: given orally once daily in 28 day cycles


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Patients must have documented histological or cytological evidence of adenocarcinoma of the prostate. Patients must have a minimum serum PSA level of >2 ng/ml that is rising based on the Prostate Cancer Working Group 2 criteria. Patients must have castrate levels of testosterone (<50 ng/dl [1.74 nmol/l]). Patients must have undergone orchiectomy, or have been on LHRH agonists or antagonists, for at least 3 months prior to study entry. Patients on LHRH agonists/antagonists must remain on these agents for the duration of the study. Patients must have an ECOG Performance Score of 0 or 1. Key Exclusion Criteria: Patients who have received prior cytotoxic chemotherapy for castration-resistant prostate cancer unless enrolled in a previous chemotherapy cohort. Patients who have received second-line antihormonal therapy, including ketoconazole, aminoglutethimide, or high-dose estrogen within 30 days of study entry. Patients who have completed sipuleucel-T (Provenge ®) treatment within 30 days of study entry. Patients who have received TOK-001 (Galeterone®) or any other investigational product directed towards the androgen receptor or androgen biosynthesis. Patients who have received antiandrogens such as flutamide (EULEXIN®), bicalutamide (CASODEX®), or nilutamide (NILANDRON®) for > 3 months must be off treatment for 6 weeks and demonstrate a continued rise in PSA after withdrawal. Patients on antiandrogens for < 3 months must be off medication for 2 weeks. Patients on 5 alpha reductase inhibitors such as finasteride (PROSCAR®, PROPECIA®), or dutasteride (AVODART®) must stop medication at least 3 months from study entry. Patients who require pharmacological or replacement doses of systemic corticosteroids or who have received systemic corticosteroids within 30 days of study entry; use of topical, inhaled or ophthalmic steroids is permitted. Patients who have received palliative radiotherapy within 4 weeks of study entry. Patients with a history within the last 3 years of another invasive malignancy.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Regimen 1: 7dayPM+DT<br>VT-464: given orally once daily in 28 day cycles. Dosing in the evening before bed 7-days a week with a 2-week dose titration. | Drug: VT-464: given orally once daily in 28 day cycles<br>* VT-464: given orally once daily in 28 day cycles either 5 days or 7 days a week.<br>* Other names: VT-464;|
| Experimental: Regimen 2: 7dayPM-DT<br>VT-464: given orally once daily in 28 day cycles. Dosing in the evening before bed 7-days a week without dose titration. | Drug: VT-464: given orally once daily in 28 day cycles<br>* VT-464: given orally once daily in 28 day cycles either 5 days or 7 days a week.<br>* Other names: VT-464;|
| Experimental: Regimen 3: 7dayAM+DT<br>VT-464: given orally once daily in 28 day cycles. Dosing in the morning 7-days a week with a 2-week dose titration. | Drug: VT-464: given orally once daily in 28 day cycles<br>* VT-464: given orally once daily in 28 day cycles either 5 days or 7 days a week.<br>* Other names: VT-464;|
| Experimental: Regimen 4: 7dayAM-DT<br>VT-464: given orally once daily in 28 day cycles.Dosing in the morning 7-days a week without dose titration. | Drug: VT-464: given orally once daily in 28 day cycles<br>* VT-464: given orally once daily in 28 day cycles either 5 days or 7 days a week.<br>* Other names: VT-464;|
| Experimental: Regimen 5: 5dayPM-DT<br>VT-464: given orally once daily in 28 day cycles.Dosing in the evening before bed 5-days a week without dose titration. | Drug: VT-464: given orally once daily in 28 day cycles<br>* VT-464: given orally once daily in 28 day cycles either 5 days or 7 days a week.<br>* Other names: VT-464;|
| Experimental: Regimen 6: 5dayAM-DT<br>VT-464: given orally once daily in 28 day cycles.Dosing in the morning 5-days a week without dose titration. | Drug: VT-464: given orally once daily in 28 day cycles<br>* VT-464: given orally once daily in 28 day cycles either 5 days or 7 days a week.<br>* Other names: VT-464;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The safety and tolerability of VT-464 by evaluating adverse events, vital signs, physical examination findings, concomitant medications and laboratory tests. |  | The first 28-day continuous dosing cycle at target dose. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Plasma Concentration (Cmax) of VT-464 |  | After the first dose of VT-464 | 
| Area under the plasma concentration versus time curve (AUC) of VT-464 |  | After the first dose of VT-464 | 
| Time to maximum plasma concentration (Tmax) of VT-464 |  | After the first dose of VT-464 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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castration-resistant prostate cancer, CYP17, P450c17a, lyase