A Study of EPI-7386 in Combination With Abiraterone Acetate Plus Prednisone, or Apalutamide in Metastatic Castration-resistant Prostate Cancer (mCRPC)
Study Details
Study Description
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Group A: EPI-7386 + Abiraterone Acetate Plus Prednisone (AAP) Participants with metastatic castration-resistant prostate cancer (mCRPC) will receive EPI-7386 + AAP to determine the recommended phase 2 dose (RP2D) dose of EPI-7386 in combination with AAP in dose finding portion of the study. In dose expansion portion of the study, participants will receive EPI-7386 RP2D in combination with AAP. |
Drug: EPI-7386
EPI-7386 will be administered orally once daily.
Drug: Abiraterone Acetate
Abiraterone Acetate will be administered orally once daily.
Drug: Prednisone or Prednisolone
Prednisone or Prednisolone will be administered orally twice daily.
|
| Experimental: Group B: EPI-3786 + Apalutamide Participants with mCRPC will receive EPI-7386 + apalutamide to determine RP2D dose of EPI-7386 in combination with apalutamide in dose finding portion of the study. In dose expansion portion of the study, participants will receive EPI-7386 RP2D in combination with apalutamide. |
Drug: EPI-7386
EPI-7386 will be administered orally once daily.
Drug: Apalutamide
Apalutamide will be administered orally once daily.
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Histologically confirmed prostate adenocarcinoma
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Must be able to continue Gonadotropin-releasing hormone agonist (GnRHa) during the study if not surgically castrate
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Eastern Cooperative Oncology Group (ECOG) performance status grade of 0, 1, or 2
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Must be able to swallow oral medicines
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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
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Willing and able to adhere to the prohibitions and restrictions specified in this protocol
Exclusion Criteria:
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Known central nervous system (CNS) metastases
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Non-metastatic castration-resistant prostate cancer (CRPC) (biochemical or locoregional disease only) is excluded from trial participation
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Evidence of predominant neuroendocrine/small cell carcinoma features in archival or baseline tumor biopsy specimen(s)
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Symptomatic or impending spinal cord compression, except if participant has received definitive treatment and demonstrates evidence of clinically stable disease
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Known disorder affecting gastrointestinal absorption
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Cedars- Sinai Medical Center | Los Angeles | California | United States | 90048 |
| 2 | University of California San Francisco | San Francisco | California | United States | 94158-2549 |
| 3 | Mayo Clinic - Division Of Hematology/oncology | Jacksonville | Florida | United States | 32224 |
| 4 | Chesapeake Urology Research Associates | Towson | Maryland | United States | 21204 |
| 5 | Dana-Farber Cancer Institute | Boston | Massachusetts | United States | 02115 |
| 6 | Washington University School of Medicine | Saint Louis | Missouri | United States | 63110 |
| 7 | GU Research Network | Omaha | Nebraska | United States | 68130 |
| 8 | New York University Langone Medical Center | New York | New York | United States | 10016 |
| 9 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10065 |
| 10 | Thomas Jefferson University | Philadelphia | Pennsylvania | United States | 19107 |
| 11 | Carolina Urologic Research Center | Myrtle Beach | South Carolina | United States | 29572 |
| 12 | University of Utah Huntsman Cancer Institute | Salt Lake City | Utah | United States | 84112 |
| 13 | Prostate Cancer Centre | Calgary | Alberta | Canada | T2V 1P9 |
| 14 | British Columbia Cancer Agency (BCCA) - Vancouver Centre | Vancouver | British Columbia | Canada | V5Z 4E6 |
| 15 | Sunnybrook Health Sciences Centre | Toronto | Ontario | Canada | M4N 3M5 |
| 16 | Princess Margaret Hospital | Toronto | Ontario | Canada | M5G 2M9 |
| 17 | Centre Hospitalier de l'Universite de Montreal | Montreal | Quebec | Canada | H2X 0A9 |
| 18 | Arensia Exploratory Medicine | Tbilisi | Georgia | Postal code 0112 | |
| 19 | Arensia Exploratory Medicine - Clinical Republican Hospital | Chisinau | Moldova, Republic of | MD-2025 | |
| 20 | Hosp. Univ. Vall D Hebron | Barcelona | Spain | 08035 | |
| 21 | Hosp. Gral. Univ. de Castellon | Castello de la Plana | Spain | 12002 | |
| 22 | Hosp. Univ. Fund. Jimenez Diaz | Madrid | Spain | 28040 |
Sponsors and Collaborators
- Janssen Research & Development, LLC
Investigators
- Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CR109122
- 81712917PCR2001