The purpose of this study is to determine safety, including dose limiting toxicities, and the recommended phase 2 dose (RP2D) of EPI-7386 in separate combinations with (a) abiraterone acetate plus prednisone or prednisolone (AAP) and (b) apalutamide (dose-finding) and to determine the antitumor activity of EPI-7386 in separate combinations with (a) AAP and (b) apalutamide (dose-expansion).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
3
EPI-7386 will be administered orally once daily.
Abiraterone Acetate will be administered orally once daily.
Prednisone or Prednisolone will be administered orally twice daily.
Chesapeake Urology Research Associates
Towson, Maryland, United States
GU Research Network
Omaha, Nebraska, United States
Carolina Urologic Research Center
Myrtle Beach, South Carolina, United States
Prostate Cancer Centre
Calgary, Alberta, Canada
Number of Participants with Adverse Events (AEs)
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.
Time frame: Up to 3 Years 3 Months
Number of Participants with AEs by Severity
Number of participants with AEs by severity will be reported.
Time frame: Up to 3 Years 3 Months
Number of Participants with Dose-limiting Toxicities (DLT)
The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity.
Time frame: Up to 28 days of Cycle 1 (each cycle of 28 days)
Composite Response Rate
Composite response rate at 12 weeks, defined as either 90 percent (%) reduction in prostate-specific antigen (PSA) level from baseline (PSA-90), or objective response (confirmed per Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1) in participants with measurable disease, or both at 12 weeks.
Time frame: At 12 weeks
Maximum Observed Serum Concentration (Cmax) of EPI-7386 and Abiraterone
Cmax is defined as the maximum observed serum concentration of EPI-7386 and abiraterone.
Time frame: Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
Time to Reach Maximum Observed Serum Concentration (Tmax) of EPI-7386 and Abiraterone
Tmax is defined as the time to reach maximum observed serum concentration of EPI-7386 and abiraterone.
Time frame: Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Apalutamide will be administered orally once daily.
Area Under the Curve From Time Zero to tau (AUC[0-tau]) of EPI-7386 and Abiraterone
AUC(0-tau) is defined as area under the curve from time 0 to tau hours post dose of EPI-7386 and abiraterone.
Time frame: Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
Minimum Observed Serum Concentration (Cmin) of EPI-7386 and Abiraterone
Cmin is the minimum observed serum concentration of EPI-7386 and abiraterone.
Time frame: Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
Observed Accumulation Index Based on Cmax (ARCmax) of EPI-7386 and Abiraterone
The observed accumulation ratio for Cmax, determined after multiple dose administration of EPI-7386 and abiraterone (Cycle\[C\] 2 Day\[D\] 1/C1D1 and C3D1/C1D1).
Time frame: Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
Accumulation Ratio for AUCtau (AR AUCtau) of EPI-7386 and Abiraterone
The observed accumulation ratio for AUCtau, determined after multiple dose administration of EPI-7386 and abiraterone (C2D1/C1D1 and C3D1/C1D1).
Time frame: Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
Maximum Observed Serum Concentration (Cmax) of EPI-7386 and Apalutamide
Cmax is defined as the maximum observed serum concentration of EPI-7386 and apalutamide.
Time frame: Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
Time to Reach Maximum Observed Serum Concentration (Tmax) of EPI-7386 and apalutamide
Tmax is defined as the time to reach maximum observed serum concentration of EPI-7386 and apalutamide.
Time frame: Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
Area Under the Curve From Time Zero to tau (AUC[0-tau]) of EPI-7386 and Apalutamide
AUC(0-tau) is defined as area under the curve from time 0 to tau hours post dose of EPI-7386 and apalutamide.
Time frame: Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
Minimum Observed Serum Concentration (Cmin) of EPI-7386 and Apalutamide
Cmin is the minimum observed serum concentration of EPI-7386 and apalutamide.
Time frame: Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
Observed Accumulation Index Based on Cmax (ARCmax) of EPI-7386 and Apalutamide
The observed accumulation ratio for Cmax, determined after multiple dose administration EPI-7386 and apalutamide (C2D1/C1D1 and C3D1/C1D1).
Time frame: Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
Accumulation Ratio for AUCtau (AR AUCtau) of EPI-7386 and Apalutamide
The observed accumulation ratio for AUCtau, determined after multiple dose administration EPI-7386 and Apalutamide (C2D1/C1D1 and C3D1/C1D1).
Time frame: Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
Serum Prostate-Specific Antigen (PSA)
Serum PSA concentration will be measured.
Time frame: Up to 3 Years 3 Months