Clinical trial NCT03741712: A Study of SHR2554 Alone or in Combination With SHR3680 in the Treatment of mCRPC
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Prostate Cancer
Castration-resistant Prostate Cancer
Keywords: Castration-resistant Prostate Cancer
SHR2554
SHR3680
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2018-11-15
Enrollment: 9
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: DLT
timeFrame: Approximately 12 months
measure: MTD
timeFrame: Approximately 12 months
measure: PSA response rate
timeFrame: Approximately 12 weeks
Secondary outcomes:
measure: Time to PSA progression
timeFrame: Approximately 70 months
measure: Objective response rate (ORR)
timeFrame: Approximately 70 months
measure: Under the Curve (AUC)
timeFrame: Approximately 12 months
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: Approximately 12 months
measure: Adverse events (AE)
timeFrame: Approximately 70 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
Study officials:
affiliation: Fudan University
name: Dingwei Ye, M.D.
role: PRINCIPAL_INVESTIGATOR
References: