A Phase I/II,Open-Label,Does-Escalation and -Expansion, Safety,Pharmacokinetics and Efficacy Study of SHR2554 Alone or in Combination With SHR3680 in the Treatment of Patients With Metastatic Castration Resistant Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- DLT
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed prostate cancer;
- •Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1;
- •Radiographic evidence of metastasis;
- •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;
- •Evidence of prostate cancer progression under the sustained therapy of LHRHA or bilateral orchiectomy;
- •Adequate hepatic, renal, heart, and hematological functions;
- •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performance of any study-related procedure not part of normal medical care,with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
排除标准
- •Have received any anti-tumor therapy in the past 4 weeks,including radiotherapy, chemotherapy, operation, targeted therapy, immunotherapy, and endocrinotherapy;
- •Planned to initiate any other anti-tumor therapies during the study;
- •Unable to swallow, chronic diarrhea and intestinal obstruction, or the presence of a variety of other factors that affect drug use and absorption;
- •Clinically significant cardiovascular diseases;
- •History of seizure or certain conditions that may predispose to seizure;
- •Severe concurrent disease and infection that, in the judgment of the investigator, would make the patient inappropriate for enrollment.
研究组 & 干预措施
SHR2554
Participants will receive SHR2554 orally
干预措施: SHR2554 (Drug)
SHR2554+SHR3680
Participants will receive SHR2554 combined with SHR3680 orally
干预措施: SHR3680 (Drug)
SHR2554+SHR3680
Participants will receive SHR2554 combined with SHR3680 orally
干预措施: SHR2554 (Drug)
结局指标
主要结局
DLT
时间窗: Approximately 12 months
A DLT is any of the predefined set of unacceptable adverse events observed and at least possibly related to investigational agents
PSA response rate
时间窗: 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%
MTD
时间窗: 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
次要结局
- Time to PSA progression(Approximately 70 months)
- Maximum Observed Plasma Concentration (Cmax)(Approximately 12 months)
- Objective response rate (ORR)(Approximately 70 months)
- Under the Curve (AUC)(Approximately 12 months)
- Adverse events (AE)(Approximately 70 months)