Prostate Cancer, Castration-resistant Prostate Cancer
Conditions
Keywords
Castration-resistant Prostate Cancer, SHR2554, SHR3680
Brief summary
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.
Detailed description
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.
Interventions
Sponsors
Jiangsu HengRui Medicine Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically or cytologically confirmed prostate cancer; 2. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1; 3. Radiographic evidence of metastasis; 4. Sustained therapy of luteinizing hormone-releasing hormone analogue（LHRHA）or received bilateral orchiectomy; patients who did not receive bilateral orchiectomy are willing to receive sustained therapy of LHRHA; 5. Evidence of prostate cancer progression under the sustained therapy of LHRHA or bilateral orchiectomy; 6. Adequate hepatic, renal, heart, and hematological functions; 7. Patients have given voluntary written informed consent before performance of any study-related procedure not part of normal medical care,with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
Exclusion criteria
1. Have received any anti-tumor therapy in the past 4 weeks,including radiotherapy, chemotherapy, operation, targeted therapy, immunotherapy, and endocrinotherapy; 2. Planned to initiate any other anti-tumor therapies during the study; 3. Unable to swallow, chronic diarrhea and intestinal obstruction, or the presence of a variety of other factors that affect drug use and absorption; 4. Clinically significant cardiovascular diseases; 5. History of seizure or certain conditions that may predispose to seizure; 6. Severe concurrent disease and infection that, in the judgment of the investigator, would make the patient inappropriate for enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| DLT | Approximately 12 months | A DLT is any of the predefined set of unacceptable adverse events observed and at least possibly related to investigational agents |
| MTD | Approximately 12 months | 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 |
| PSA response rate | Approximately 12 weeks | 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% |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) | Approximately 12 months | The single-dose and multiple dose PK will be calculated as data permits including Cmax |
| Time to PSA progression | Approximately 70 months | Time from randomisation to the first time of PSA progression according to the criteria of the Prostate Cancer Clinical Trials Working Group 3 （PCWG3) |
| Adverse events (AE) | Approximately 70 months | The type, frequency, severity, timing, seriousness, and relationship to study therapy |
| Objective response rate (ORR) | Approximately 70 months | 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 |
| Under the Curve (AUC) | Approximately 12 months | The single dose and multiple dose PK will be calculated as data permits including Area AUC |
Countries
China
Outcome results
None listed