Prostatic Neoplasms
Conditions
Brief summary
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).
Interventions
DRUGEPI-7386
EPI-7386 will be administered orally once daily.
DRUGAbiraterone Acetate
Abiraterone Acetate will be administered orally once daily.
Prednisone or Prednisolone will be administered orally twice daily.
DRUGApalutamide
Apalutamide will be administered orally once daily.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed prostate adenocarcinoma * Must be able to continue Gonadotropin-releasing hormone agonist (GnRHa) during the study if not surgically castrate * Eastern Cooperative Oncology Group (ECOG) performance status grade of 0, 1, or 2 * Must be able to swallow oral medicines * Contraceptive use by men (and female partners of men enrolled in the study who are of childbearing potential or are pregnant) (birth control) use should be consistent with local regulations regarding the use of contraceptive methods for participants participating in clinical studies * Willing and able to adhere to the prohibitions and restrictions specified in this protocol
Exclusion criteria
* Known central nervous system (CNS) metastases * Non-metastatic castration-resistant prostate cancer (CRPC) (biochemical or locoregional disease only) is excluded from trial participation * Evidence of predominant neuroendocrine/small cell carcinoma features in archival or baseline tumor biopsy specimen(s) * Symptomatic or impending spinal cord compression, except if participant has received definitive treatment and demonstrates evidence of clinically stable disease * Known disorder affecting gastrointestinal absorption
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Adverse Events (AEs) | Up to 3 Years 3 Months | 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. |
| Number of Participants with AEs by Severity | Up to 3 Years 3 Months | Number of participants with AEs by severity will be reported. |
| Number of Participants with Dose-limiting Toxicities (DLT) | Up to 28 days of Cycle 1 (each cycle of 28 days) | The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity. |
| Composite Response Rate | At 12 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Serum Concentration (Cmax) of EPI-7386 and Abiraterone | Day 1 of each cycle up to 3 cycles (each cycle of 28 days) | Cmax is defined as the maximum observed serum concentration of EPI-7386 and abiraterone. |
| Time to Reach Maximum Observed Serum Concentration (Tmax) of EPI-7386 and Abiraterone | Day 1 of each cycle up to 3 cycles (each cycle of 28 days) | Tmax is defined as the time to reach maximum observed serum concentration of EPI-7386 and abiraterone. |
| Area Under the Curve From Time Zero to tau (AUC[0-tau]) of EPI-7386 and Abiraterone | Day 1 of each cycle up to 3 cycles (each cycle of 28 days) | AUC(0-tau) is defined as area under the curve from time 0 to tau hours post dose of EPI-7386 and abiraterone. |
| Minimum Observed Serum Concentration (Cmin) of EPI-7386 and Abiraterone | Day 1 of each cycle up to 3 cycles (each cycle of 28 days) | Cmin is the minimum observed serum concentration of EPI-7386 and abiraterone. |
| Observed Accumulation Index Based on Cmax (ARCmax) of EPI-7386 and Abiraterone | Day 1 of each cycle up to 3 cycles (each cycle of 28 days) | 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). |
| Accumulation Ratio for AUCtau (AR AUCtau) of EPI-7386 and Abiraterone | Day 1 of each cycle up to 3 cycles (each cycle of 28 days) | The observed accumulation ratio for AUCtau, determined after multiple dose administration of EPI-7386 and abiraterone (C2D1/C1D1 and C3D1/C1D1). |
| Maximum Observed Serum Concentration (Cmax) of EPI-7386 and Apalutamide | Day 1 of each cycle up to 3 cycles (each cycle of 28 days) | Cmax is defined as the maximum observed serum concentration of EPI-7386 and apalutamide. |
| Time to Reach Maximum Observed Serum Concentration (Tmax) of EPI-7386 and apalutamide | Day 1 of each cycle up to 3 cycles (each cycle of 28 days) | Tmax is defined as the time to reach maximum observed serum concentration of EPI-7386 and apalutamide. |
| Area Under the Curve From Time Zero to tau (AUC[0-tau]) of EPI-7386 and Apalutamide | Day 1 of each cycle up to 3 cycles (each cycle of 28 days) | AUC(0-tau) is defined as area under the curve from time 0 to tau hours post dose of EPI-7386 and apalutamide. |
| Minimum Observed Serum Concentration (Cmin) of EPI-7386 and Apalutamide | Day 1 of each cycle up to 3 cycles (each cycle of 28 days) | Cmin is the minimum observed serum concentration of EPI-7386 and apalutamide. |
| Observed Accumulation Index Based on Cmax (ARCmax) of EPI-7386 and Apalutamide | Day 1 of each cycle up to 3 cycles (each cycle of 28 days) | The observed accumulation ratio for Cmax, determined after multiple dose administration EPI-7386 and apalutamide (C2D1/C1D1 and C3D1/C1D1). |
| Accumulation Ratio for AUCtau (AR AUCtau) of EPI-7386 and Apalutamide | Day 1 of each cycle up to 3 cycles (each cycle of 28 days) | The observed accumulation ratio for AUCtau, determined after multiple dose administration EPI-7386 and Apalutamide (C2D1/C1D1 and C3D1/C1D1). |
| Serum Prostate-Specific Antigen (PSA) | Up to 3 Years 3 Months | Serum PSA concentration will be measured. |
Countries
Canada, United States
Outcome results
None listed