Metastatic Castration-resistant Prostate Cancer, Prostate Cancer, Prostate Carcinoma
Conditions
Keywords
HRR, Olaparib, mCRPC
Brief summary
This is a multi-center, single-arm, prospective study to assess the efficacy and safety of Olaparib in men with newly diagnosed metastatic castration-resistant prostate cancer (mCRPC) who carried homologous recombination repair (HRR) gene mutations and have progressed after treatment with novel endocrine agents (NHA) in the metastatic castration-sensitive prostate cancer or non-metastatic castration-resistant prostate cancer. A total of 30 newly diagnosed mCRPC subjects with radiologically evaluable disease at baseline who have progressed on prior NHA and carry HRR gene mutations that meet the criteria will be included in the study. Eligible subjects will receive a treatment regimen of oral Olaparib tablets 300 mg twice daily until disease progression or intolerance. During the treatment and follow-up periods, all subjects will have regular visits to assess the efficacy and safety of Olaparib. Data on objective radiographic response (ORR), prostate-specific antigen response (PSA response), radiographic progression-free survival (rPFS), and time to prostate-specific antigen progression (TTPP) will be collected during the study.
Interventions
DRUGOlaparib
Lynparza (Olaparib tablets) 300 mg should be taken orally twice daily
Sponsors
AstraZeneca
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
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 0-2. 4. Histologically confirmed adenocarcinoma of the prostate. 5. Subjects must have previously received NHA (e.g., abiraterone acetate and/or enzalutamide) for mHSPC or nmCRPC and have disease progression to mCRPC. Disease progression was determined by the local investigator based on the diagnostic criteria for mCRPC (CRPC diagnostic criteria: testosterone maintained at castrate levels (testosterone levels less than 50 ng/dL or 1.7 nmol/L) while meeting at least one of the following criteria: A. biochemical progression: three consecutive rising PSA with an interval of at least one week between the two tests, more than 50% increase from the nadir, and PSA \> 2 ng/mL; B. radiographic progression: new lesions: two or more new bone lesions on bone scan or one soft tissue lesion meeting the RECIST criteria. Symptomatic progression alone is not sufficient to diagnose CRPC. Established radiographic evidence of metastatic disease in addition to CRPC to confirm the diagnosis of mCRPC). 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 at least 1 measurable lesion at baseline (according to RECIST 1.1 criteria: At least one lesion, not previously irradiated, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and which is suitable for accurate repeated measurements). 9. Subjects must have at least 1 qualifying HRR gene mutation in tumor tissue and/or plasma ct-DNA confirmed 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. 10. Subjects must have normal organ and bone marrow function at baseline, as defined below: * Hemoglobin ≥ 10.0 g/dL without previous transfusion. * 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). 11. Male subject has been surgically sterilized or uses an acceptable method of contraception (defined as a barrier method with spermicide) to prevent pregnancy during the duration of the study and for 12 weeks after the dose of prednisone. 12. Subjects must have a life expectancy ≥ 16 weeks. 13. 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 |
|---|---|---|
| Primary Outcome Measures 3 | up to 60 months | PSA response will be reported in ng/mL (≥ 50% reduction in PSA from baseline) according to PCWG 3 criteria as determined by the local investigator |
| Primary Outcome Measures 1 | up to 60 months | 1\. To assess the efficacy of Olaparib in newly diagnosed metastatic castration-resistant prostate cancer with mutations in homologous recombination repair genes that have progressed after prior treatment with novel endocrine agents. -The Overall response rate will be based on the following outcome definitions and a patient will be considered a response if any of these occur: (1) Objective response (ORR) according to RECIST 1.1 (soft tissue) |
| Primary Outcome Measures 2 | up to 60 months | Objective response (ORR) according to PCWG-3 (bone) criteria as determined by the local investigator |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary Outcome Measures 3 | up to 60 months | Investigator-assessed confirmed the time to PSA progression (TTPP) per PCWG3 |
| Secondary Outcome Measures 1 | up to 60 months | Investigator-assessed confirmed radiographic progression-free survival (rPFS) will be reported in weeks per RECIST 1.1 (soft tissue) and PCWG3 (bone) |
| Secondary Outcome Measures 2 | up to 60 months | Investigator-assessed confirmed disease control rate (DCR) per RECIST 1.1 (soft tissue) and PCWG3 (bone) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Other Outcome Measures | up to 60 months | To explore the concordance rate of tissue samples and plasma ct-DNA samples by second-generation sequencing (NGS) testing -Concordance rate between tissue and plasma ct-DNA testing results |
Countries
China
Contacts
Primary ContactHao Liu
Outcome results
None listed