A Phase 1/2 Open-Label Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Seviteronel in Subjects With Castration-Resistant Prostate Cancer
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Castration-resistant Prostate Cancer
- Sponsor
- Innocrin Pharmaceutical
- Enrollment
- 200
- Locations
- 23
- Primary Endpoint
- Proportion of subjects who have ≥50% PSA decline at any time on study from the start of treatment with seviteronel.
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief Summary
The goal of this clinical study is to determine the safety, tolerability, pharmacokinetics and activity of Seviteronel, a lyase-selective inhibitor of CYP17, in patients with castration-resistant prostate cancer (CRPC).
Detailed Description
This is a Phase 1/2 study of seviteronel in subjects with castration-resistant prostate cancer (CRPC). Phase 1 was a dose-escalation study enrolling subjects with CRPC that were either "treatment naïve" (not treated with previous abiraterone or enzalutamide), or treated with one or more of the following: abiraterone, enzalutamide, or chemotherapy. Phase 2 is an open-label, multi-center cohort-expansion study to further determine the efficacy and safety of seviteronel in two CRPC populations with documented rising PSA with or without bone or soft tissue disease progression during treatment with: abiraterone or enzalutamide for ≥ 12 weeks (Group 1) abiraterone and enzalutamide; treatment should be ≥ 12 weeks for at least one agent (Group 2)
Investigators
Eligibility Criteria
Inclusion Criteria
- •1.18 years of age or older
- •Able to provide written informed consent or have their legal representatives provide written informed consent
- •Documented histological or cytological evidence of adenocarcinoma of the prostate. Subjects whose pathology reports are no longer available may be enrolled if, in the opinion of the investigator, the subject has a clinical course consistent with prostatic adenocarcinoma
- •ECOG Performance Status of 0 or 1
- •Undergone orchiectomy, or have ongoing LHRH analogue therapy prior to C1D
- •Subjects on LHRH analogues should remain on these agents for the duration of the study
- •Castrate levels of testosterone less than or equal to 50 ng/dl (or 1.7 nmol/L) and have progressive disease at Screening defined as PSA rise determined by a minimum of 2 rising PSA values greater than or equal to 1 week between each assessment. The PSA value at the Screening visit must be greater than or equal 2ng/mL with or without: Soft tissue disease progression defined by RECIST 1.1 at Screening or less than or equal to 28 days of C1D
- •Measurable disease is not required for entry.
- •Lymph nodes greater than or equal to 1.5cm (short axis) are considered measurable disease bone disease progression defined by greater than or equal 2 new lesions on bone scan at Screening, or less than or equal 28 days of C1D1
- •Have received abiraterone and/or enzalutamide. Subject must have received either abiraterone or enzalutamide for greater than or equal to 12 weeks. Other second generation CYP17 inhibitors/androgen receptor antagonists including but not limited to TAK-700 (orteronel), TOK-001 (galeterone) may have been taken in place of abiraterone and ARN-509 (apalutamide) may have been taken in place of enzalutamide.
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
Proportion of subjects who have ≥50% PSA decline at any time on study from the start of treatment with seviteronel.
Time Frame: 6 months
Review of subjects with defined PSA value decline of greater than or equal to 50% from study start.
Median time to radiographic disease progression evaluated by computerized tomography (CT scan) or magnetic resonance imaging (MRI) and radionuclide bone scans by RECIST 1.1
Time Frame: 10 months
Review of subject disease progression status via CT and measure of median time to progression if progression occurs.
Secondary Outcomes
- Radiographic response rate by RECIST 1.1 & PCWG3. Safety of seviteronel with or without concurrent glucocorticoid administration(10 months)