A Study of SHR3680 in Combination With SHR3162 in the Treatment of mCRPC

A Phase II Clinical Study of SHR3680 Combined With SHR3162 in the Treatment of Metastatic Castration-resistant Prostate Cancer Previously Treated With Abiraterone and Docetaxel

The aim of this trial is to evaluate SHR3680 combined with SHR3162 and SHR3680 single drug to improve Metastatic Castration Resistant Prostate Cancer Patients whether the patient's overall survival (OS) is superior to placebo.

Study Overview

• Status: Unknown
• Conditions: Prostate Cancer; Castration-resistant Prostate Cancer
• Intervention / Treatment: Drug: SHR3680; Drug: SHR3162; Drug: SHR3162(Placebo); Drug: SHR3680(Placebo)

Detailed Description

This is a multicenter, randomized , double-blind Phase II trial and the aim of this trial is to evaluate SHR3680 combined with SHR3162 and SHR3680 single drug to improve Metastatic Castration Resistant Prostate Cancer Patients Previously Treated With Abiraterone and Docetaxel whether the patient's overall survival (OS) is superior to placebo. The Stage I part is a dose-escalation and -expansion study. Approximately 18~24 patients in Stage I will receive fixed-dose of orally SHR3680 and only one of two dose levels of orally SHR3162. The Primary endpoints of the Stage I are incidence of adverse events(AE) and recommended phase 2 dose(RP2D). The Stage II part is a randomized , double-blind study. Approximately 90~120 patients in Stage II will receive SHR3162 combined with SHR3680, in which one fixed-dose levels of SHR3162 will be selected based on the result of the Stage I.The Primary endpoint of the Stage II is overall survival(OS).

• Study Type: Interventional
• Enrollment (Anticipated): 144
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • Ye Dingwei

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 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; does not suggest neuroendocrine or small cell characteristics
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 patient at any time without prejudice to future medical care.
8. Patient has been treated with Abiraterone and treatment failed（Treatment failure is defined as the progression of disease during treatment）
9. Patient has been treated with Docetaxel and treatment failed or can not tolerate docetaxel chemotherapy or patients who are not suitable for docetaxel treatment at the time of screening.

Exclusion Criteria:

1. Have received any anti-tumor therapy in the past 4 weeks,including radiotherapy, chemotherapy, operation, targeted therapy, immuntherapy, 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: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SHR3680+SHR3162; Participants will receive SHR3680 combined with SHR3162 orally	Drug: SHR3680; Tablet. Specifications of 80mg; Drug: SHR3162; Tablet. Specifications of 10mg、40mg、50mg and 100mg
Experimental: SHR3680+SHR3162(Placebo); Participants will receive SHR3680 combined with SHR3162(Placebo) orally	Drug: SHR3680; Tablet. Specifications of 80mg; Drug: SHR3162(Placebo); Tablet. Specifications of 10mg、40mg、50mg and 100mg
Placebo Comparator: SHR3680(Placebo)+SHR3162(Placebo); Participants will receive SHR3680(Placebo) combined with SHR3162(Placebo) orally	Drug: SHR3162(Placebo); Tablet. Specifications of 10mg、40mg、50mg and 100mg; Drug: SHR3680(Placebo); Tablet. Specifications of 80mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Event(AE)	The type, frequency, severity, timing, seriousness, and relationship to study therapy	Approximately 70 months
Overall Survival(OS)	Time from randomisation to death due to any cause	Approximately 70 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to prostate specific antigen (PSA) progression	Time from randomisation to the first time of PSA progression according to the criterion of PCGW3	Approximately 70 months
Radiographic Progression Free Survival(rPFS)	Time from randomisation to radiologically confirmed progressive disease or death due to any cause	Approximately 70 months
Objective response rate (ORR)	The percentage of patients 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 skeletal-related events	Time from randomisation to the first occurrence of a skeletal-related event. The skeletal-related event is defined as the occurrence of either pathological or clinical fracture, spinal cord compression, bone-related radiotherapy or surgery.	Approximately 70 months
PSA response rate	After the continuous therapy from randomisation to the end of the 12 weeks, the percentage of patients whose levels of PSA decreased by more than 50% compared with baseline.	Approximately 70 months
Area Under the Curve (AUC)	The single dose and multiple dose PK will be calculated as data permits including 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
Minimum Observed Plasma Concentration (Cmin)	The single-dose and multiple dose PK will be calculated as data permits including Cmin	Approximately 12 months

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2019
• Primary Completion (Anticipated): November 1, 2021
• Study Completion (Anticipated): November 1, 2022

Study Registration Dates

• First Submitted: September 23, 2019
• First Submitted That Met QC Criteria: September 23, 2019
• First Posted (Actual): September 25, 2019

Study Record Updates

• Last Update Posted (Actual): May 14, 2020
• Last Update Submitted That Met QC Criteria: May 12, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Castration-resistant Prostate Cancer; SHR3680; SHR3162
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: SHR3680-SHR3162-II-CRPC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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