Metastatic Castration-Resistant Prostate Cancer MedDRA version: 21.1 Level: PT Classification code 10036909 Term: Prostate cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: LLT Classification code 10076506 Term: Castration-resistant prostate cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 100
Conditions
Interventions
Product Name: Fuzuloparib
Product Code: SHR3162
Pharmaceutical Form: Capsule
INN or Proposed INN: Fuzuloparib
CAS Number: 1358715-18-0
Current Sponsor code: SHR3162
Other descriptive name: Fluzoparib
Sponsors
Jiangsu Hengrui Medicine Co., Ltd
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1) Age of = 18 years old. 2) A score of 0 to 1 for ECOG performance status. 3) Expected survival of = 6 months. 4) Prostate adenocarcinoma confirmed by histology or cytology examinations, with no indication of neuroendocrine differentiation or small cell characteristics. 5) Metastatic lesions with imaging evidence. 6) Disease progression of metastatic prostate cancer while the subject was on androgen deprivation therapy. See the disease progression at study entry definition in the protocol. 7) Continuous treatment with luteinizing hormone-releasing hormone analogue (LHRHa) (drug-induced castration) or previous bilateral orchidectomy (surgical castration); subjects who have not undergone bilateral orchidectomy must plan to maintain effective LHRHa treatment within 4 weeks prior to the randomization of this study and throughout the entire study. 8) Testosterone is at the castration level (= 50 ng/dL or 1.73 nmol/L) during screening. 9) Blood and tumor tissue samples (tumor sample is optional) are provided during screening to determine the DRD status; subjects in Cohort 2 must be DRD positive. 10) The functional level of the organs must meet the requirements (no blood transfusion or treatment with hematopoietic growth factor within 2 weeks prior to routine blood screening) as detailed in the protocol. 11) For patients who are judged by the investigator as having the ability to ejaculate and who are sexually active must agree to take effective contraceptive measures and not to donate sperm from the first dose to 3 months after the last dose of study treatment. 12) Participate in this clinical trial voluntarily, understand and have signed the informed consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 482 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 322
Exclusion criteria
Exclusion criteria: 1) Prior treatment with any PARP inhibitor. 2) Have received any systemic anti-tumor treatment during the mCRPC stage or non-metastatic CRPC (nmCRPC) stage, including chemotherapy, immunotherapy, abiraterone acetate or other CYP17 inhibitors, novel AR antagonists (such as enzalutamide, apalutamide, darolutamide, SHR3680, and proxalutamide) and other molecular targeted therapies. See protocol for the allowed exceptions. 3) With severe bone injury caused by bone metastasis of prostate cancer as judged by the investigator, including poorly controlled severe bone pain, and pathological fractures and spinal cord compressions that have occurred in the last 6 months before the first dose or are expected to occur soon. 4) Radiotherapy or major surgery within 3 weeks before the first dose, or participation in other drug clinical trials within 4 weeks or 5 half-lives, whichever is longer, prior to start of this study drug at day 1 (C1D1). 5) Have used any strong/moderate CYP3A4 inducers or inhibitors within 14 days prior to the first dose. 6) The use of drugs that may affect P-gp cannot be interrupted during the study. 7) Plan to receive any other anti-tumor treatment during the study treatment of this study. 8) Presence of radiologically confirmed tumor lesions in the brain. 9) Contraindications to the use of prednisone (corticosteroids), such as active infections or other medical conditions. 10) Any chronic medical conditions that require a dose of corticosteroid = 5 mg prednisone BID. 11) History of uncontrolled pituitary or adrenal dysfunction. 12) Uncontrolled hypertension (persistent systolic blood pressure = 160 mmHg or diastolic blood pressure = 100 mmHg). Subjects with a history of hypertension are allowed to participate in the study if their blood pressure can be effectively controlled by antihypertensive therapy. 13) Presence of active heart diseases (including severe/unstable angina pectoris, symptomatic congestive heart failure of NYHA Class III or IV, left ventricular ejection fraction < 50%, and ventricular arrhythmia requiring drug therapy) or a history of arterial or venous thrombosis (including pulmonary embolism and cerebrovascular accident) within 6 months, or myocardial infarction within 12 months prior to the first dose. 14) History of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML), or a history of other malignant tumors within 5 years prior to the first dose (except carcinoma in situ that has been completely relieved and the malignant tumor that is judged by investigators as slowly progressive). 15) Active HBV or HCV infection (HBsAg positive with virus copy = 500 IU/mL, HCV antibody positive with HCV RNA higher than the lower limit of detection of the analytical method). 16) Human immunodeficiency virus-positive subjects with 1 or more of the following: - Not receiving highly active antiretroviral therapy. - Had a change in antiretroviral therapy within 6 months of the start of screening. - Receiving antiretroviral therapy that may interfere with study drug (consult sponsor for review of medication prior to enrollment). - CD4 count < 350/mm3 at screening. - AIDS-defining opportunistic infection within 12 months of start of screening. 17) Presence of dysphagia, chronic diarrhea, intestinal obstruction, or other factors affecting drug intake and absorption. 18) With known allergy or intolerance to fuzuloparib, abiraterone acetate, prednisone, or their excipients. 19) Confirmed SARS-CoV-2
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To evaluate whether fuzuloparib plus AA-P is superior to placebo plus AA-P as first-line treatment by assessment of rPFS in mCRPC subjects unselected for DRD status (Cohort 1) - To evaluate whether fuzuloparib plus AA-P is superior to placebo plus AA-P as first-line treatment by assessment of rPFS in mCRPC subjects harboring DRD (Cohort 2);Secondary Objective: To evaluate the OS in unselected mCRPC subjects (Cohort 1) and in mCRPC subjects harboring DRD (Cohort 2), respectively.;Primary end point(s): - Cohort 1: rPFS (assessed by Blinded Independent Central Review (BICR) according to RECIST 1.1 and PCWG3 criteria) in unselected mCRPC subjects. - Cohort 2: rPFS (assessed by Blinded Independent Central Review (BICR) according to RECIST 1.1 and PCWG3 criteria) in mCRPC subjects harboring DRD.;Timepoint(s) of evaluation of this end point: At predetermined time points as described in the protocol. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - OS in unselected mCRPC subjects (Cohort 1) and in mCRPC subjects harboring DRD (Cohort 2), respectively.;Timepoint(s) of evaluation of this end point: At predetermined time points as described in the protocol. | — |
Countries
Australia, Belgium, China, Czechia, Czech Republic, France, Hungary, Korea, Republic of, Poland, Russian Federation, Spain, Taiwan, United Kingdom, United States
Contacts
Public ContactChunlei Jin, M.D
Jiangsu Hengrui Medicine Co., Ltd
Outcome results
None listed