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

Innocrin Pharmaceutical

Status and phase: Completed; Phase 2; Phase 1

Conditions: Castration-resistant Prostate Cancer; CRPC

Treatments: Drug: VT-464: given orally once daily in 28 day cycles

Study type: Interventional

Funder types: Industry

Identifiers

NCT02361086

INO-VT-464-CL-004

Details and patient eligibility

About

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).

Full 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.

Enrollment: 21 patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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21 participants in 6 patient groups

Regimen 1: 7dayPM+DT

Experimental group

Description:

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.

Treatment:

Drug: VT-464: given orally once daily in 28 day cycles

Regimen 2: 7dayPM-DT

Experimental group

Description:

VT-464: given orally once daily in 28 day cycles. Dosing in the evening before bed 7-days a week without dose titration.

Treatment:

Drug: VT-464: given orally once daily in 28 day cycles

Regimen 3: 7dayAM+DT

Experimental group

Description:

VT-464: given orally once daily in 28 day cycles. Dosing in the morning 7-days a week with a 2-week dose titration.

Treatment:

Drug: VT-464: given orally once daily in 28 day cycles

Regimen 4: 7dayAM-DT

Experimental group

Description:

VT-464: given orally once daily in 28 day cycles.Dosing in the morning 7-days a week without dose titration.

Treatment:

Drug: VT-464: given orally once daily in 28 day cycles

Regimen 5: 5dayPM-DT

Experimental group

Description:

VT-464: given orally once daily in 28 day cycles.Dosing in the evening before bed 5-days a week without dose titration.

Treatment:

Drug: VT-464: given orally once daily in 28 day cycles

Regimen 6: 5dayAM-DT

Experimental group

Description:

VT-464: given orally once daily in 28 day cycles.Dosing in the morning 5-days a week without dose titration.

Treatment:

Drug: VT-464: given orally once daily in 28 day cycles