A Single-center, Single-arm, Prospective Study to Investigate the Efficacy and Safety of Olaparib Combined With Abiraterone and Prednisone in mHSPC Patients With HRR Gene Mutation
Overview
- Phase
- Phase 2
- Intervention
- Olaparib tablet
- Conditions
- Prostate Cancer
- Sponsor
- Hongqian Guo
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- 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
- Status
- Recruiting
- Last Updated
- 3 years ago
Overview
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.
Investigators
Hongqian Guo
Director of Urology Department
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Eligibility Criteria
Inclusion Criteria
- •For inclusion in the study, subjects should fulfil the following criteria based on local regulations:
- •Provision of informed consent prior to any study specific procedures.
- •Adult male patients (age≥18 years old).
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •Histologically confirmed adenocarcinoma of the prostate.
- •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.
- •The subject had a serum testosterone level ≤ 50 ng/dL (≤ 1.75 nmol/L) before enrollment.
- •Patients who have not undergone previous surgery must be taking and voluntarily continue taking LHRH analogues (agonists or antagonists) throughout the study treatment period.
Exclusion Criteria
- •Subjects should not enter the study if any of the following exclusion criteria are fulfilled:
- •Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site) .
- •Previous enrolment in the present study.
- •Subjects participated in another clinical study with a drug or plan to participate in another interventional clinical study within 30 days prior to enrollment.
- •Prior treatment with any PARP inhibitor or any new hormone agent, including Olaparib, Niraparib, Abiraterone, Enzalutamide, Apalutamide, etc.
- •Prior chemotherapy with any DNA-damaging cytotoxic agent unless used to treat non-prostate cancer and the last dose was at least 5 years prior to enrollment in this study. For example: Patients previously treated with mitoxantrone or platinum-based chemotherapy for prostate cancer are excluded.
- •Patients who have received prior chemotherapy with any taxane. For example, patients who have received prior Docetaxel for prostate cancer are excluded.
- •Other malignancies within the last 5 years.
- •History of adrenal dysfunction.
- •Presence of persistent uncontrolled hypertension (systolic blood pressure \> 160 mmHg or diastolic blood pressure \> 100 mmHg). Subjects with a history of hypertension are allowed to participate if blood pressure could be controlled within these limits by antihypertensive therapy.
Arms & Interventions
Intervention/Treatment
Subjects will receive a regimen of Olaparib tablets 300 mg twice daily in combination with Abiraterone acetate 1000 mg plus Prednisone 5mg once daily until radiographic disease progression (assessed by the investigator according to RECIST1.1 and PCWG3) or intolerable adverse events (assessed by the investigator according to the actual clinical situation).
Intervention: Olaparib tablet
Intervention/Treatment
Subjects will receive a regimen of Olaparib tablets 300 mg twice daily in combination with Abiraterone acetate 1000 mg plus Prednisone 5mg once daily until radiographic disease progression (assessed by the investigator according to RECIST1.1 and PCWG3) or intolerable adverse events (assessed by the investigator according to the actual clinical situation).
Intervention: Abiraterone acetate
Intervention/Treatment
Subjects will receive a regimen of Olaparib tablets 300 mg twice daily in combination with Abiraterone acetate 1000 mg plus Prednisone 5mg once daily until radiographic disease progression (assessed by the investigator according to RECIST1.1 and PCWG3) or intolerable adverse events (assessed by the investigator according to the actual clinical situation).
Intervention: Prednisone tablet
Outcomes
Primary Outcomes
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
Time Frame: 18 month
Time from the start of study drug to radiographic progression, or death due to any cause, whichever occurs first.
Secondary Outcomes
- PSA response rate(18 month)
- PSA Progression Free Survival (PSA-PFS) by Investigator(18 month)
- Confirmed Objective Response Rate (ORR) by Investigator(18 month)