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

Sponsor

Innocrin Pharmaceutical (Industry)

Overall Status

Completed

CT.gov ID

NCT02361086

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

4.2

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Castration-resistant Prostate Cancer CRPC	Drug: VT-464: given orally once daily in 28 day cycles	Phase 1/Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

21 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Jun 1, 2014

Actual Primary Completion Date :

Dec 1, 2017

Actual Study Completion Date :

Jun 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Regimen 1: 7dayPM+DT 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 VT-464: given orally once daily in 28 day cycles either 5 days or 7 days a week. Other Names: VT-464
Experimental: Regimen 2: 7dayPM-DT 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 VT-464: given orally once daily in 28 day cycles either 5 days or 7 days a week. Other Names: VT-464
Experimental: Regimen 3: 7dayAM+DT 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 VT-464: given orally once daily in 28 day cycles either 5 days or 7 days a week. Other Names: VT-464
Experimental: Regimen 4: 7dayAM-DT 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 VT-464: given orally once daily in 28 day cycles either 5 days or 7 days a week. Other Names: VT-464
Experimental: Regimen 5: 5dayPM-DT 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 VT-464: given orally once daily in 28 day cycles either 5 days or 7 days a week. Other Names: VT-464
Experimental: Regimen 6: 5dayAM-DT 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 VT-464: given orally once daily in 28 day cycles either 5 days or 7 days a week. Other Names: VT-464

Outcome Measures

Primary Outcome Measures

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

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 Outcome Measures

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]
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida	United States	33612
2	Urology Cancer Center	Omaha	Nebraska	United States	68130
3	Duke University Medical Center	Durham	North Carolina	United States	27710
4	Carolina Urologic Research Center	Myrtle Beach	South Carolina	United States	29572
5	Virginia Oncology Associates	Norfolk	Virginia	United States	23502