Oral VT-464 in Patients With Castration-Resistant Prostate Cancer Previously Treated With Enzalutamide, Androgen Receptor Positive Triple-Negative Breast Cancer Patients, and Men With ER Positive Breast Cancer

A Phase 2 Open-Label Study to Evaluate the Efficacy and Safety of VT-464 in Patients With Metastatic Castration Resistant Prostate Cancer Who Have Previously Been Treated With Enzalutamide, Androgen Receptor Positive Triple-Negative Breast Cancer Patients, and Men With ER Positive Breast Cancer

The goal of this clinical study is to determine the safety and efficacy of VT-464, a lyase-selective inhibitor of CYP17, in patients with castration-resistant prostate cancer (CRPC) who have been previously treated with Enzalutamide, Androgen Receptor Positive Triple-Negative Breast Cancer Patients, and Men with ER positive Breast Cancer.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: VT-464: given orally twice daily in 28-day cycles; Drug: VT-464: given orally once daily in 28-day cycles

Detailed Description

This is a Phase 2 open-label study of VT-464 in patients with progressive, metastatic castration-resistant prostate cancer (mCRPC) who have been previously treated with enzalutamide, female patients with triple negative, AR positive breast cancer and men with ER positive breast cancer. The study consists of five cohorts: patients in Cohort 1 must have never received prior chemotherapy. Patients in Cohort 2 must have received at least one (and not more) prior course of chemotherapy for CRPC. Women with TNBC will be stratified into two cohorts AR 1 to 9% (cohort 3) and AR > 10% (cohort 4). Cohort 5 will consist of men who have been diagnosed with ER+ breast cancer and have failed at least one prior endocrine therapy.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health, National Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Key Eligibility Criteria:

• Patients must have documented histological or cytological evidence of adenocarcinoma of the prostate.
• Must have progressive, metastatic castration-resistant prostate cancer (mCRPC). There must be radiographic evidence of disease after primary treatment with surgery or radiotherapy that has continued to progress radiographically or biochemically (rising PSA levels on successive measurements) despite adequate androgen-deprivation therapy, which is defined as having undergone bilateral surgical castration or continued treatment on GnRH agonists or antagonists.
• All patients in this trial must have been treated with enzalutamide.
• Patients in Cohort 1 will not be allowed to have received prior chemotherapy; patients in Cohort 2 must have received one (and not more) prior course of chemotherapy for mCRPC.

• Progression must be evidenced and documented by any of the following parameters:

  • PSA progression defined by a minimum of two rising PSA levels with an interval of ≥ 1 week between each determination
  • Appearance of one or more new lesions on bone scan
  • Progressive measurable disease by RECIST 1.1

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Chemotherapy-Naive Patients; VT-464: given orally twice daily in 28-day cycles	Drug: VT-464: given orally twice daily in 28-day cycles; Oral VT-464 given twice daily, in continuous 28-day cycles at the recommended Phase 2 dose; Other Names: VT-464
Experimental: Previous Chemotherapy Patients; VT-464: given orally twice daily in 28-day cycles	Drug: VT-464: given orally twice daily in 28-day cycles; Oral VT-464 given twice daily, in continuous 28-day cycles at the recommended Phase 2 dose; Other Names: VT-464
Experimental: AR Positive 1 - 9% TNBC; VT-464: given orally once daily in 28-day cycles	Drug: VT-464: given orally once daily in 28-day cycles; Oral VT-464 given once daily, in continuous 28-day cycles at the recommended Phase 2 dose; Other Names: seviteronel
Experimental: Male ER Positive; VT-464: given orally once daily in 28-day cycles	Drug: VT-464: given orally once daily in 28-day cycles; Oral VT-464 given once daily, in continuous 28-day cycles at the recommended Phase 2 dose; Other Names: seviteronel
Experimental: AR Positive >10% TNBC; VT-464: given orally once daily in 28-day cycles	Drug: VT-464: given orally once daily in 28-day cycles; Oral VT-464 given once daily, in continuous 28-day cycles at the recommended Phase 2 dose; Other Names: seviteronel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change in PSA from baseline using waterfall plots in response to 12-weeks of treatment with VT-464	To determine the PSA response as defined by a ≥ 50% decrease in serum PSA per the Prostate Cancer Clinical Trials Working Group 2 criteria after each cycle and after 12 weeks of dosing with VT-464 compared to PSA level at baseline in patients who have been previously treated with enzalutamide.	12 weeks
Progression-free survival using Kaplan-Meier curves	Kaplan-Meier curves of progression-free survival (PFS) will be constructed in each cohort and the median PFS will be determined and informally compared to any available results.	8 months
Determine clinical benefit rate (CBR) as defined by complete response (CR), partial response (PR) or stable disease (SD) in women with androgen receptor (AR) positive, triple-negative breast cancer	Clinical benefit rate will be measured at designated timepoints as listed per protocol	16 weeks
Determine clinical benefit rate (CBR) as defined by complete response (CR), partial response (PR) or stable disease (SD) in women with androgen receptor (AR) positive, triple-negative breast cancer	Clinical benefit rate will be measured at designated timepoints as listed per protocol	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival using Kaplan-Meier curves	Overall Survival: will be analyzed similarly to PFS, with a separate Kaplan-Meier curve for each arm. A patient for whom there is no death event will be censored; the censored date will be the date of last contact.	32 months
The safety and tolerability of VT-464 by evaluating adverse events, vital signs, physical examination findings, concomitant medications and laboratory tests.	The safety of VT-464 will be evaluated by laboratory evaluation, electrocardiogram, the report of adverse events and concomitant medications at each 28-day cycle of treatment and 4-5 weeks after therapy has been discontinued.	8 months
Maximum PSA response compared to baseline	Maximum PSA response will be descriptive in nature and presented for each cohort as a percent of patients and as a waterfall plot.	8 months

Collaborators and Investigators

• Sponsor: Innocrin Pharmaceutical
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): September 1, 2017
• Study Completion (Actual): November 1, 2017

Study Registration Dates

• First Submitted: April 22, 2014
• First Submitted That Met QC Criteria: May 1, 2014
• First Posted (Estimate): May 5, 2014

Study Record Updates

• Last Update Posted (Actual): May 7, 2018
• Last Update Submitted That Met QC Criteria: May 2, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: mCRPC; metastatic; castration-resistant prostate cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Breast Diseases; Prostatic Diseases; Breast Neoplasms; Prostatic Neoplasms; Triple Negative Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Cytochrome P-450 Enzyme Inhibitors; Seviteronel
• Other Study ID Numbers: INO-VT-464-CL-002; VMT-VT-464-CL-002 (Other Identifier: Innocrin)