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
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
285
Our lady of Lourdes Urology
Binghamton, New York, United States
Princess Alexandra Hospital
Brisbane, Australia
Cabrini Hospital
Melbourne, Australia
Macquarie University Hospital
Sydney, Australia
rPFS assessed by BICR
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).
Time frame: 80 weeks
rPFS assessed by BICR
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.
Time frame: 80 weeks
Time to pain progression
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 frame: 80 weeks
Time from randomization to the first SSRE
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.
Time frame: 80 weeks
OS
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.
Time frame: 80 weeks
PFS2
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.
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John Flynn Hospital
Tugun, Australia
IMPACT Therapeutics Inc.
Shanghai, Shanghai Municipality, China
Time frame: 80 weeks
Time to pain progression
To evaluate the impact of Senaparib on time to pain progression, compared with the placebo, in mCRPC patients with HRR gene alterations who have not progressed after docetaxel therapy.
Time frame: 80 weeks
Time from randomization to the first SSRE
To evaluate the impact of Senaparib on time to the first SSRE, compared with the placebo, in mCRPC patients with HRR gene alterations who have not progressed after docetaxel therapy.
Time frame: 80 weeks
OS
To evaluate the impact of Senaparib on OS, compared with the placebo, in mCRPC patients with HRR gene alterations who have not progressed after docetaxel therapy.
Time frame: 80 weeks
rPFS assessed by the investigator
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.
Time frame: 80 weeks
Time to PSA progression
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.
Time frame: 80 weeks
Objective response rate (ORR) according to RECIST v1.1 assessed by BICR
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.
Time frame: 80 weeks
Objective response rate (ORR) according to RECIST v1.1 assessed by investigator
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.
Time frame: 80 weeks
PSA response rate according to PCWG3 criteria assessed by central laboratory
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.
Time frame: 80 weeks
Safety endpoints
Number of participants with treatment-related adverse events as assessed by NCI CTCAE v5.0.
Time frame: 80 weeks
Cmax
Maximum plasma concentration,To characterize the plasma PK profile of Senaparib via population PK (popPK) modeling
Time frame: 80 weeks