Castration-resistant Prostate Cancer, CRPC
Conditions
Keywords
castration-resistant prostate cancer, CYP17, P450c17a, lyase
Brief summary
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
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.
Interventions
DRUGVT-464: given orally once daily in 28 day cycles
VT-464: given orally once daily in 28 day cycles either 5 days or 7 days a week.
Sponsors
Innocrin Pharmaceutical
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | 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
| Measure | 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 |
Other
| Measure | Time frame |
|---|---|
| Objective tumor response to VT-464 at the end of even-numbered cycles using RECIST 1.1 criteria | At least every other month over the first 8 28-day dosing cycles |
| The absolute and percent change from baseline in adrenal, pituitary, and testicular hormone concentrations in response to VT-464 | At least monthly over the first 8 28-day dosing cycles |
| The change in PSA from baseline using waterfall plots in response to VT-464 | At least monthly over the first 8 28-day dosing cycles |
Countries
United States
Outcome results
None listed