mCRPC
Conditions
Interventions
Dose escalation:HSK46575 3 mg~160 mg:co-administered with glucocorticoid and fludrocortisone, orally daily
Dose expansion:HSK46575 with RP2D:co-administered with glucocorticoid and fludrocortisone, orally daily
Sponsors
West China Hospital of Sichuan University
Eligibility
Sex/Gender
Male
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1) >=18 years old, male; 2) ECOG 0 ~ 1 score; 3) Expected survival >=3 months; 4) Prostate adenocarcinoma confirmed by histology or cytology; 5) Metastatic bone or soft tissue lesions with imaging evidence; 6) Prior surgical castration, or stable drug castration prior to initial administration, and plan to remain stable throughout the study period; 7) At the time of screening, testosterone was at castration level (<=50 ng/dL or 1.73 nmol/L); 8) Pre-screening subjects received ADT (drug castration or surgical castration) at a time when there was clear evidence of disease progression; 9) Progress after prior NHA treatment and progress after prior taxane chemotherapy; 10) The functional level of organs must conform to the program; 11) Subjects who are sexually active and have the ability to ejaculate must agree to use medically approved contraceptive methods (such as barrier contraception, abstinence, etc.) and not donate sperm for 3 months from the first dose of the study to the last dose; 12) Voluntarily participate in this clinical trial, understand the research procedure and have signed the informed consent.
Exclusion criteria
Exclusion criteria: 1) Known to be allergic to the active ingredients or excipients of HSK46575 tablets; 2) Use of any other antitumor therapy (except castration) within 4 weeks prior to initial administration (or 5 half-lives, whichever is shorter); Or received nitrosylureas, bicalutamide, or nilumide within 6 weeks (or 5 half-lives, whichever is shorter) prior to first administration; 3) Before the first administration of the drug, the toxic reactions caused by previous anti-tumor therapy were still > grade 1, except for reactions that the investigators judged did not pose a safety risk (such as hair loss, skin pigmentation, etc.); 4) Received radiation therapy within 4 weeks before the first dose; 5) Use of CYP3A4 potent and intermediate-acting inhibitors or inducers within 14 days or 5 half-lives prior to the first administration of the study drug, whichever is longer; 6) In subjects treated with bisphosphonates or drugs such as desumab or dinomumab for bone metastases or bone-related diseases, irregular or inconsistent medication within 4 weeks prior to the first dose; 7) Subjects who had undergone grade 3-4 surgery within 4 weeks prior to initial dosing; Use of botanicals or supplements that may lower PSA levels within 4 weeks prior to initial dosing; 8) Plan to receive any other anti-tumor therapy during the treatment period of this study except as prescribed in the protocol; 9) Patients with active central nervous system metastases with imaging evidence. 10) Severe bone damage from bone metastases of prostate cancer as determined by the investigators; 11) Pituitary or adrenal dysfunction within 6 months prior to initial administration; 12) Combined with uncontrolled hypertension; 13) Patients with central nervous system diseases such as epilepsy, multiple sclerosis and other diseases; 14) The presence of active heart disease or arterial or venous thromboembolism within 6 months prior to the first dose; 15) The QTc interval calculated by Fridericia formula during the screening period was extended to >470 ms; 16) Combined with other malignant tumors; 17) Combined history of immune deficiency; 18) Have active HBV, HCV or syphilis infection; 19) Subjects who are not expected to be evaluated for bone metastasis progression; 20) The presence of dysphagia, chronic diarrhea, intestinal obstruction, or other factors affecting drug administration and absorption within 1 month before the first dose of the study; 21) Participate in other clinical trials within 4 weeks before the first dose; 22) Concomitant disease or any other condition that, in the judgment of the investigator, seriously endangers the safety of the subject or interferes with the completion of the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Adverse events occurring throughout the study period were assessed.;To explore the dose-limiting toxicity of HSK46575 tablets;PK parameters of HSK46575; | — |
Secondary
| Measure | Time frame |
|---|---|
| PSA changes at week 12;PSA response rate;Time to PSA progression;Objective relief rate, ORR;Modified Best Overall Response,mBOR, mBOR;Disease control rate, DCR;overall surviva, OS;Time to the first symptomatic bone-related event;PD parameters of HSK46575; | — |
Countries
China
Contacts
Public ContactFeng ping/ Wei qiang
West China Hospital of Sichuan University
Outcome results
None listed