Prostate Cancer, Prostate Carcinoma, Metastatic Prostate Cancer
Conditions
Keywords
HRR, Olaparib, mCSPC
Brief summary
This is a single-center, single-arm, prospective study to assess the efficacy and safety of Olaparib combined with Abiraterone plus Prednisone in subjects with metastatic hormone sensitive prostate cancer (mHSPC) who carry deleterious germline or homologous recombination repair (HRR) mutations. Olaparib is an oral, highly selective poly (ADP-ribose) polymerase (PARP) inhibitor that potently inhibits the activity of deoxyribonucleic acid repair polymerases. Abiraterone acetate (AA) is a prodrug of abiraterone that potently inhibits cytochrome P450c17, a key enzyme in androgen biosynthesis. A total of 30 mHSPC subjects with HRR gene mutations that meet the criteria will be included in the study. Eligible subjects will receive oral Olaparib tablets 300 mg BID, combined with Abiraterone acetate 1000 mg QD plus Prednisone 5 mg, and the study will end when the primary endpoint radiographic progression-free survival (rPFS) data maturity reaches 60%. During the treatment and follow-up periods, all subjects will have regular visits to assess the efficacy and safety of Olaparib in combination with abiraterone acetate plus prednisone. Radiographic progression-free survival (rPFS), prostate-specific antigen response (PSA response rate), prostate-specific antigen progression-free survival (PSA-PFS), radiological objective response rate (ORR) and other indicators will be assessed and calculated.
Interventions
DRUGOlaparib tablet
Lynparza (Olaparib tablets) 300 mg should be taken orally twice daily.
DRUGAbiraterone acetate
Qingkeshu (Abiraterone acetate tablets) 1000 mg should be taken orally once daily.
Prednisone Tablets should be taken 5 mg once daily.
Sponsors
AstraZeneca
Nanjing Chia-tai Tianqing Pharmaceutical
Hongqian Guo
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
For inclusion in the study, subjects should fulfil the following criteria based on local regulations: 1. Provision of informed consent prior to any study specific procedures. 2. Adult male patients (age≥18 years old). 3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. 4. Histologically confirmed adenocarcinoma of the prostate. 5. Subjects must have at least 1 qualifying HRR gene mutation in tumor tissue by central lab (Glorious Med, shanghai, China). * Archival or new biopsies are acceptable. * Qualifying HRR gene mutations (deleterious or suspected deleterious gene alterations) are BRCA1, BRCA2, ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, RAD51B, RAD 51C, RAD51D and RAD54L mutations confirmed by the central lab. 6. The subject had a serum testosterone level ≤ 50 ng/dL (≤ 1.75 nmol/L) before enrollment. 7. Patients who have not undergone previous surgery must be taking and voluntarily continue taking LHRH analogues (agonists or antagonists) throughout the study treatment period. 8. Subjects must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below: * Hemoglobin ≥ 10.0 g/dL without previous transfusion within 28 days. * Absolute neutrophil count ≥ 1.5 × 10\^9/L. * Platelet count ≥ 100 × 10\^9/L. * Total bilirubin ≤ 1.5 × the upper limit of normal (ULN) specified. * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase/alanine aminotransferase (ALT) serum glutamic pyruvic transaminase) ≤ 2.5 × the specified ULN, unless liver metastases are present, in which case it must be ≤ 5 × ULN. * Estimated creatinine clearance ≥ 51 mL/min (estimated creatinine clearance = \[140 - age (years)\] × weight (kg)/(serum creatinine (mg/dL)×72)). 9. Male patients must use a condom during treatment and for 12 weeks after the last dose of Olaparib when having sexual intercourse with a pregnant woman or with a woman of childbearing potential. Female partners of male patients should also use a highly effective form of contraception (\[see appendix C for acceptable methods\]) if they are of childbearing potential 10. Subjects must have a life expectancy ≥ 16 weeks. 11. The subjects must volunteer and be capable of complying with the protocol for the duration of the study, including receiving treatment, attending scheduled visits and hospital examinations.
Exclusion criteria
Subjects should not enter the study if any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Radiographic Progression-Free Survival (rPFS) Per Prostate Cancer Working Group (PCWG)-modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator | 18 month | Time from the start of study drug to radiographic progression, or death due to any cause, whichever occurs first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PSA response rate | 18 month | PSA response is defined as a ≥ 50% decline in PSA from baseline PSA value. This PSA decline must be confirmed as sustained by a second PSA value obtained ≥ 3 weeks later. |
| PSA Progression Free Survival (PSA-PFS) by Investigator | 18 month | PSA-PFS is defined as the time from the start of study drug to the first PSA progression or death due to any cause without progression. PSA progression is defined as a first PSA increase greater than or equal to 25% of baseline and ≥ 2 ng/ml and confirmed a second time after 3 or more weeks. |
| Confirmed Objective Response Rate (ORR) by Investigator | 18 month | ORR is the percentage of patients with at least one visit response of Complete response (CR) or Partial response (PR), in their soft tissue disease assessed by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), in the absence of progression on bone scan assessed by Prostate Cancer Working Group 3 (PCWG3)). Per RECIST v1.1, CR=Disappearance of all target lesions; PR = \>=30% decrease in the sum of diameters of target lesions; For each treatment group, ORR is the number of patients with a CR and PR. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experience an Adverse Event (AE) | 18 month | An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment |
Countries
China
Outcome results
None listed