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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: VT-464: given orally twice daily in 28-day cycles
* Drug: VT-464: given orally once daily in 28-day cycles


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mCRPC, metastatic, castration-resistant prostate cancer