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

Castration-resistant Prostate Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02361086
• Other study ID #: INO-VT-464-CL-004
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: June 2014
• Est. completion date: June 2018

Study information

• Verified date: January 2019
• Source: Innocrin Pharmaceutical
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: June 2018
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Castration-resistant Prostate Cancer
• CRPC
• Prostatic Neoplasms

Intervention

Drug:
• VT-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.

Locations

Country	Name	City	State
United States	Duke University Medical Center	Durham	North Carolina
United States	Carolina Urologic Research Center	Myrtle Beach	South Carolina
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	Urology Cancer Center	Omaha	Nebraska
United States	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Innocrin Pharmaceutical

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Primary	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	Peak Plasma Concentration (Cmax) of VT-464		After the first dose of VT-464
Secondary	Area under the plasma concentration versus time curve (AUC) of VT-464		After the first dose of VT-464
Secondary	Time to maximum plasma concentration (Tmax) of VT-464		After the first dose of VT-464