A Study of SHR2554 Alone or in Combination With SHR3680 in the Treatment of mCRPC

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

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.

Study Overview

• Status: Terminated
• Conditions: Prostate Cancer; Castration-resistant Prostate Cancer
• Intervention / Treatment: Drug: SHR3680; Drug: SHR2554

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.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China
      • Fudan University Shanghai Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: SHR2554; Participants will receive SHR2554 orally	Drug: SHR2554; Tablet. Specifications of 50mg and 200mg
EXPERIMENTAL: SHR2554+SHR3680; Participants will receive SHR2554 combined with SHR3680 orally	Drug: SHR3680; Tablet. Specifications of 80mg; Drug: SHR2554; Tablet. Specifications of 50mg and 200mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma Concentration (Cmax)	The single-dose and multiple dose PK will be calculated as data permits including Cmax	Approximately 12 months
Objective response rate (ORR)	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
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
Under the Curve (AUC)	The single dose and multiple dose PK will be calculated as data permits including Area AUC	Approximately 12 months
Adverse events (AE)	The type, frequency, severity, timing, seriousness, and relationship to study therapy	Approximately 70 months

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 20, 2018
• Primary Completion (ACTUAL): September 30, 2019
• Study Completion (ACTUAL): December 8, 2020

Study Registration Dates

• First Submitted: October 17, 2018
• First Submitted That Met QC Criteria: November 12, 2018
• First Posted (ACTUAL): November 15, 2018

Study Record Updates

• Last Update Posted (ACTUAL): February 5, 2021
• Last Update Submitted That Met QC Criteria: February 2, 2021
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: Castration-resistant Prostate Cancer; SHR3680; SHR2554
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: SHR2554-SHR3680-I/II-102

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No