A Multi-center, Single-arm, Prospective Study to Investigate the Efficacy and Safety of Olaparib Monotherapy in Newly Diagnosed mCRPC Patients Who Progressed on NHA and With HRR Gene Mutation
Overview
- Phase
- Phase 2
- Intervention
- Olaparib
- Conditions
- Prostate Cancer
- Sponsor
- Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Primary Outcome Measures 1
- Last Updated
- 4 years ago
Overview
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.
Investigators
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 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).
- •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.
- •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).
- •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)
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 including Olaparib.
- •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.
- •Other malignancies within the last 5 years.
- •Uncontrolled or underlying cardiac disease on resting electrocardiogram (eg, but not limited to: unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QT prolongation \> 500 ms with Fridericia correction, congenital long QT syndrome).
- •The subject had received any systemic anticancer therapy (except radiotherapy) 3 weeks prior to study treatment.
- •Medications used to maintain castrate status were permitted as described in Inclusion Criteria
Arms & Interventions
Intervention/Treatment
Subjects will receive a regimen of Olaparib tablets 300 mg twice daily until radiographic disease progression (assessed by the investigator according to RECIST1.1 and PCWG 3) or intolerable adverse events (assessed by the investigator according to the actual clinical situation).
Intervention: Olaparib
Outcomes
Primary Outcomes
Primary Outcome Measures 1
Time Frame: 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
Time Frame: up to 60 months
Objective response (ORR) according to PCWG-3 (bone) criteria as determined by the local investigator
Primary Outcome Measures 3
Time Frame: 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
Secondary Outcomes
- Secondary Outcome Measures 1(up to 60 months)
- Secondary Outcome Measures 2(up to 60 months)
- Secondary Outcome Measures 3(up to 60 months)