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

Study Overview
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Brief Summary
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The aim of this trial is to evaluate SHR3680 combined with Docetaxel to improve Metastatic Castration Resistant Prostate Cancer Patients whether the patient's Time to prostate specific antigen (PSA) progression is superior to SHR3680 or Docetaxel single drug.

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

Conditions
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Prostate Cancer Metastatic

Intervention / Treatment
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* Drug: SHR3680+Docetaxel
* Drug: SHR3680
* Drug: Docetaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed prostate cancer; Unconfirmed neuroendocrine carcinoma or small cell carcinoma; Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1; Radiographic evidence of metastasis（CT/MRI/ECT); 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performance of any study-related procedure not part of normal medical care,with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care； Expected to survive for at least 3 months； Patient has been treated with Abiraterone and treatment failed；Treatment failure is defined as the progression of disease during treatment； Exclusion Criteria: Have received any anti-tumor therapy in the past 4 weeks,including radiotherapy, chemotherapy, operation, targeted therapy, immuntherapy, and endocrinotherapy; As a subject to participate in other drug clinical trials, the last test drug was administered within 4 weeks from the first dose of the study drug; Plan to receive any other anti-tumor treatment during this trial; Subjects have contraindications to prednisone, such as active infections or other conditions; Subjects present any chronic condition requiring treatment with corticosteroids at doses greater than prednisone 5 mg, BID; The investigators judged severe bone damage caused by tumor bone metastasis, including severely controlled bone pain, pathological fractures and spinal cord compressions that occurred in the last 6 months or are expected to occur in the near future; Uncontrolled high blood pressure (systolic blood pressure 160 mmHg or diastolic blood pressure 95 mmHg). If blood pressure can be effectively controlled by antihypertensive therapy, subjects with a history of hypertension are allowed to participate in the study; Study of active heart disease within 6 months prior to the first dose, including: severe/unstable angina, myocardial infarction, symptomatic congestive heart failure, left ventricular ejection fraction <50%, and room for medication Arrhythmia; Imaging diagnosis of brain tumor lesions; history of pituitary or adrenal dysfunction; Study of other malignant tumors within 5 years prior to the first dose (in situ cancer with complete remission and excluding malignant tumors with slow progress); Patients with active HBV or HCV infection (HBV virus copy number #104 copies/mL, HCV virus copy number #103 copies/mL), or active syphilis infection; History of immunodeficiency (including HIV positive, other acquired, congenital immunodeficiency disease) or organ transplant history; Habitual constipation or diarrhea, irritable bowel syndrome, inflammatory bowel disease; abdominal fistula, gastrointestinal perforation or abdominal abscess within 6 months before the first dose; Patients who are unwilling to take effective contraceptive measures during the entire study period and within 3 months after the last dose

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SHR3680+Docetaxel<br> | Drug: SHR3680+Docetaxel<br>* Participants will receive SHR3680 combined with Docetaxel<br>|
| Active Comparator: SHR3680<br> | Drug: SHR3680<br>* Participants will receive SHR3680<br>|
| Active Comparator: Docetaxel<br> | Drug: Docetaxel<br>* Participants will receive Docetaxel<br>|

What is the study measuring?
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Primary 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 | [Time Frame: Approximately 24 months] | 
| Adverse Event(AE) | The type, frequency, severity, timing, seriousness, and relationship to study therapy | [Time Frame: Approximately 24 months] | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiographic Progression Free Survival(rPFS) | Time from randomisation to radiologically confirmed progressive disease or death due to any cause | [Time Frame: Approximately 24 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 | [Time Frame: Approximately 24 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 | [Time Frame: Approximately 3 months] | 
| Overall Survival(OS) | Time from randomisation to death due to any cause | [Time Frame: Approximately 24 months] | 
| Area Under the Curve (AUC) | The single dose and multiple dose PK will be calculated as data permits including AUC | [Time Frame: Approximately 2 months] | 
| Maximum Observed Plasma Concentration (Cmax) | The single-dose and multiple dose PK will be calculated as data permits including Cmax | [Time Frame: Approximately 2 months] | 
| Minimum Observed Plasma Concentration (Cmin) | The single-dose and multiple dose PK will be calculated as data permits including Cmin | [Time Frame: Approximately 2 months] |