Clinical trial NCT02361086: A Study to Evaluate Once-Daily Oral VT-464 in Patients With Castration-Resistant Prostate Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Castration-resistant Prostate Cancer
CRPC
Keywords: castration-resistant prostate cancer
CYP17
P450c17a
lyase
Lead sponsor: Innocrin Pharmaceutical
Sponsor class: INDUSTRY
First posted: 2015-02-11
Enrollment: 21
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: The safety and tolerability of VT-464 by evaluating adverse events, vital signs, physical examination findings, concomitant medications and laboratory tests.
timeFrame: The first 28-day continuous dosing cycle at target dose.
Secondary outcomes:
measure: Peak Plasma Concentration (Cmax) of VT-464
timeFrame: After the first dose of VT-464
measure: Area under the plasma concentration versus time curve (AUC) of VT-464
timeFrame: After the first dose of VT-464
measure: Time to maximum plasma concentration (Tmax) of VT-464
timeFrame: After the first dose of VT-464
Other outcomes:
measure: The change in PSA from baseline using waterfall plots in response to VT-464
timeFrame: At least monthly over the first 8 28-day dosing cycles
measure: Objective tumor response to VT-464 at the end of even-numbered cycles using RECIST 1.1 criteria
timeFrame: At least every other month over the first 8 28-day dosing cycles
measure: The absolute and percent change from baseline in adrenal, pituitary, and testicular hormone concentrations in response to VT-464
timeFrame: At least monthly over the first 8 28-day dosing cycles
Locations:
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Omaha
country: United States
facility: Urology Cancer Center
state: Nebraska
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Myrtle Beach
country: United States
facility: Carolina Urologic Research Center
state: South Carolina
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
Study officials:
affiliation: Innocrin Pharmaceutical
name: Joel Eisner
role: STUDY_DIRECTOR
References: