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According to the available data from the trial,the sponsor determined to terminate this study.
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The aim of this trial is to study the tolerance, pharmacokinetics (PK) and efficacy of SHR2554 alone or in combination with SHR3680 in the treatment of patients with metastatic Castration Resistant Prostate Cancer.
This is a multicenter, open, non-randomized and dose-escalating and -expansion Phase I/II trial and it studies the tolerance, PK and efficacy of SHR2554 alone or in combination with SHR3680 in the treatment of patients with metastatic Castration Resistant Prostate Cancer. The Phase I part is a dose-escalating study including Ia (dose-escalation monotherapy) and Ib (dose-escalation combination therapy). Approximately 18-30 patients in Phase Ia will only receive one of five dose levels of orally SHR2554. Approximately 30~48 patients in Phase Ib trial will receive SHR2554 combined with SHR3680, in which 2~3 different dose levels of SHR2554 will be selected based on the result of the Phase Ia. Phase II part is a dose-expansion study. Primary endpoints of the study are dose-limiting tolerance (DLT), maximum-tolerated dose (MTD) and prostate specific antigen (PSA) response rate.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| SHR2554 | Experimental | Participants will receive SHR2554 orally |
|
| SHR2554+SHR3680 | Experimental | Participants will receive SHR2554 combined with SHR3680 orally |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SHR3680 | Drug | Tablet. Specifications of 80mg |
| |
| SHR2554 |
| Measure | Description | Time Frame |
|---|---|---|
| DLT | A DLT is any of the predefined set of unacceptable adverse events observed and at least possibly related to investigational agents | Approximately 12 months |
| MTD | The first cycle DLTs will be utilized to determine the MTD and future dose escalations or de-escalations The first cycle DLTs will be utilized to determine the MTD and future dose escalations or de-escalations | Approximately 12 months |
| PSA response rate | After the continuous therapy from randomisation to the end of the 12 weeks, the ratio of patients whose levels of PSA decreased more than 50% | Approximately 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Time to PSA progression | Time from randomisation to the first time of PSA progression according to the criteria of the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) | Approximately 70 months |
| Objective response rate (ORR) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Dingwei Ye, M.D. | Fudan University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fudan University Shanghai Cancer Center | Shanghai | Shanghai Municipality | China |
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| ID | Term |
|---|---|
| D011471 | Prostatic Neoplasms |
| ID | Term |
|---|---|
| D005834 | Genital Neoplasms, Male |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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| Drug |
Tablet. Specifications of 50mg and 200mg |
|
The percentage of subjects with measureable disease at baseline who achieved a complete or partial response in their soft tissue disease using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria
| Approximately 70 months |
| Under the Curve (AUC) | The single dose and multiple dose PK will be calculated as data permits including Area AUC | Approximately 12 months |
| Maximum Observed Plasma Concentration (Cmax) | The single-dose and multiple dose PK will be calculated as data permits including Cmax | Approximately 12 months |
| Adverse events (AE) | The type, frequency, severity, timing, seriousness, and relationship to study therapy | Approximately 70 months |
| D005832 |
| Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D011469 | Prostatic Diseases |
| D052801 | Male Urogenital Diseases |