mCRPC
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy and safety of Senaparib in metastatic castration-resistant prostate cancer (mCRPC) patients with homologous recombination repair (HRR) gene alterations after docetaxel treatment
Detailed description
This is a randomized, double-blinded, placebo-controlled, multicenter, Phase II study in mCRPC patients with HRR gene alterations after docetaxel therapy to evaluate the anti-tumor activity and safety of Senaparib.
Interventions
DRUGPlacebo
Senaparib-matched placebo capsules
DRUGSenaparib
20 mg capsules
Sponsors
Impact Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Randomized, Double-Blinded, Placebo-Controlled
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients must voluntarily participate in this clinical study. Be willing written informed consent form (ICF) prior to any study activity. 2. Male ≥18 years of age on the day of signing the ICF. 3. Patients must have histologically or cytologically confirmed prostate adenocarcinoma. 4. Surgically or medically castrated, with serum testosterone levels of ≤50 ng/dL (≤1.73 nmol/L). If the patient is being treated with LHRH agonists/antagonists (patient who have not undergone orchiectomy), this therapy must be continued throughout the study. 5. Patients have adequate organ functions, as indicated by the following laboratory values (had not received blood transfusion, apheresis infusion, erythropoietin, granulocyte colony-stimulating factor (G-CSF), and other relevant medical support within 14 days before the administration of study drug). 6. Patients have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. 7. Male patients must use a condom during treatment and for 3 months after the last dose of study drug when having sexual intercourse with a woman of childbearing potential. Female partners of male patients should also use an acceptable method of contraception if they are of childbearing potential.
Exclusion criteria
1. Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT). 2. Prior treatment with a polyadenosine 5'diphosphoribose polymerisation (PARP) inhibitor, including Senaparib. 3. Patients with a known hypersensitivity to Senaparib or any of the component of Senaparib. 4. Initiating bisphosphonate/denosumab therapy or adjusting bisphosphonate/denosumab dose/regimen within 28 days prior to the first dose of study drug. Patients on a stable bisphosphonate/denosumab regimen are eligible and may continue. 5. Patients who have received strong inhibitors/inducers of CYP3A4 which cannot be discontinued 21 days prior to the first dose of study drug and withheld throughout the study drug treatment. Patients received phenobarbital/enzalutamide will require a 5-week washout prior to the first dose of study drug. 6. Patients with MDS or AML, or with clinical features suggestive of MDS or AML. 7. Patients with serious acute or chronic infections. 8. Patients who have received a live virus or bacterial or RNA vaccination within 28 days prior to the first dose of study drug. 9. Patients are unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| rPFS assessed by BICR | 80 weeks | To evaluate the impact of Senaparib on radiographic progression free survival (rPFS), compared with the placebo, in metastatic castration-resistant prostate cancer (mCRPC) patients with BRCA1/2 gene alteration who have not progressed after docetaxel therapy assessed by Blinded Independent Central Review (BICR). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to pain progression | 80 weeks | To evaluate the impact of Senaparib on time to pain progression, compared with the placebo, in mCRPC patients with BRCA1/2 gene alteration who have not progressed after docetaxel therapy. |
| Time from randomization to the first SSRE | 80 weeks | To evaluate the impact of Senaparib on time to the first symptomatic skeletal related events (SSRE), compared with the placebo, in mCRPC patients with BRCA1/2 gene alteration who have not progressed after docetaxel therapy. |
| OS | 80 weeks | To evaluate the impact of Senaparib on overall survival (OS), compared with the placebo, in mCRPC patients with BRCA1/2 gene alteration who have not progressed after docetaxel therapy. |
| PFS2 | 80 weeks | To evaluate the impact of Senaparib on second progression (PFS2), compared with the placebo, in mCRPC patients with BRCA1/2 gene alteration and HRR gene alterations who have not progressed after docetaxel therapy. |
| rPFS assessed by the investigator | 80 weeks | To evaluate the impact of Senaparib on rPFS assessed by the investigator, compared with the placebo, in mCRPC patients with BRCA1/2 gene alteration and HRR gene alterations who have not progressed after docetaxel therapy. |
| rPFS assessed by BICR | 80 weeks | To evaluate the impact of Senaparib on rPFS, compared with the placebo, in mCRPC patients with homologous recombination repair (HRR) gene alterations who have not progressed after docetaxel therapy assessed by BICR. |
| Objective response rate (ORR) according to RECIST v1.1 assessed by BICR | 80 weeks | To evaluate the impact of Senaparib on radiographic response rate assessed by BICR, compared with the placebo, in mCRPC patients with BRCA1/2 gene alteration and HRR gene alterations who have measurable lesion and have not progressed after docetaxel therapy. |
| Objective response rate (ORR) according to RECIST v1.1 assessed by investigator | 80 weeks | To evaluate the impact of Senaparib on radiographic response rate assessed by the investigator, compared with the placebo, in mCRPC patients with BRCA1/2 gene alteration and HRR gene alterations who have measurable lesion and have not progressed after docetaxel therapy. |
| PSA response rate according to PCWG3 criteria assessed by central laboratory | 80 weeks | To evaluate the impact of Senaparib on PSA response rate, compared with the placebo, in mCRPC patients with BRCA1/2 gene alteration and HRR gene alterations who have not progressed after docetaxel therapy. |
| Safety endpoints | 80 weeks | Number of participants with treatment-related adverse events as assessed by NCI CTCAE v5.0. |
| Cmax | 80 weeks | Maximum plasma concentration，To characterize the plasma PK profile of Senaparib via population PK (popPK) modeling |
| Time to PSA progression | 80 weeks | To evaluate the impact of Senaparib on time to prostate-specific antigen (PSA) progression, compared with the placebo, in mCRPC patients with BRCA1/2 gene alteration and HRR gene alterations who have not progressed after docetaxel therapy. |
Countries
Australia, China, United States
Contacts
Primary Contactxingxing Zhang
Backup ContactYafei Liu
Outcome results
None listed