Clinical Study to Assess the Efficacy and Safety of Olaparib in Chinese Patients With Metastatic Castration-Resistant Prostate Cancer Who Have Failed Prior Treatment With a New Hormonal Agent and Have BRCA1/2 Mutations

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of Olaparib compared with standard of care (Enzalutamide or Abiraterone Acetate) in Chinese men with metastatic castration-resistant prostate cancer who have failed prior treatment with a new hormonal agent and have BRCA1/2 mutations.

Detailed Description
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This is a Phase IV, randomized, open-label, 2-arm, multicenter study evaluating the efficacy and safety of olaparib in Chinese men with metastatic castration-resistant prostate cancer (mCRPC) who have failed prior treatment with a new hormonal agent (NHA) and have BRCA1/2 mutations. Approximately 42 subjects will be randomized in a 2:1 ratio to olaparib or to investigator's choice of NHA (enzalutamide or abiraterone acetate).

Official Title
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A Randomized, Open-label Study to Assess the Efficacy and Safety of Olaparib Versus Enzalutamide or Abiraterone Acetate in Chinese Men With Metastatic Castration-Resistant Prostate Cancer Who Have Failed Prior Treatment With a New Hormonal Agent and Have BRCA1/2 Mutations (PROfound-CN)

Conditions
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Metastatic Castration-resistant Prostate Cancer

Intervention / Treatment
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* Drug: olaparib
* Drug: enzalutamide
* Drug: abiraterone acetate
* Drug: Prednisone


Participation Criteria
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Eligibility Criteria
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Inclusion criteria： Histologically confirmed diagnosis of prostate cancer. Documented evidence of metastatic castration resistant prostate cancer (mCRPC). Subjects must have progressed on prior new hormonal agent (e.g. abiraterone acetate and/or enzalutamide) for the treatment of metastatic prostate cancer and/or CRPC . Ongoing therapy with LHRH analog or bilateral orchiectomy. Radiological progression at study entry while on androgen deprivation therapy (or after bilateral orchiectomy). Deleterious or suspected deleterious BRCA1/2 mutation in tumor tissue. Normal organ and bone marrow function measured within 28 days prior to administration of study treatment. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 with no deterioration over the previous 2 weeks prior to baseline or day of first dosing. Exclusion criteria： Any previous treatment with a poly (adenosine diphosphate [ADP] ribose) polymerase (PARP) inhibitor, including olaparib. Subjects who had any previous treatment with DNA-damaging cytotoxic chemotherapy, except if for non-prostate cancer indication and last dose > 5 years prior to randomization. History of another primary malignancy except for malignancy treated with curative intent with no known active disease for ≥5 years before the first dose of study intervention and of low potential risk for recurrence. Spinal cord compression or brain metastases unless asymptomatic, stable, and not requiring steroids for at least 4 weeks prior to start of study intervention.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Olaparib<br>Olaparib is available as a film-coated tablet containing 150 mg or 100 mg of olaparib. Subjects will be administered study treatment orally at a dose of 300 mg twice daily (bid). The planned dose of 300 mg bid will be made up of two x 150 mg tablets twice daily, with 100 mg tablets used to manage dose reductions | Drug: olaparib<br>* 300 mg (2x 150 mg tablets) twice daily<br>* Other names: Lynparza;|
| Active Comparator: Enzalutamide OR abiraterone acetate<br>Enzalutamide: Enzalutamide is available as capsules or tablets containing 40 mg of enzalutamide. Subjects will be administered study treatment orally at a dose of 160 mg once daily. Abiraterone acetate with prednisone: Abiraterone acetate is available as tablets containing 250 mg of abiraterone acetate. Subjects will be administered study treatment orally at a dose of 1,000 mg once daily. Prednisone is 5mg twice daily. Prednisolone is permitted for use instead of prednisone if necessary. | Drug: enzalutamide<br>* 160 mg (4 x 40 mg capsules) once daily<br>* Other names: XTANDI;Drug: abiraterone acetate<br>* 1,000 mg (4 x 250 mg tablets) once daily<br>* Other names: ZYTIGA;Drug: Prednisone<br>* 5mg(5mg x 1 tablet) twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiological progression free survival (rPFS) | Radiological progression-free survival (rPFS) is defined by radiological progression, as assessed by Blinded Independent Central Review (BICR) per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) version 1.1 (soft tissue) and Prostate Cancer Working Group-3 (PCWG3) criteria (bone), or death from any cause, whichever occurs first. | From date of randomization to study completion (up to 3 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Confirmed Objective Response Rate (ORR) | Confirmed ORR is defined as a response of PR or CR in the soft tissue disease according to RECIST 1.1 in the absence of progression on bone scan and confirmed not less than 4 weeks after the initial response was observed, as assessed by BICR in patients with measurable disease using RECIST 1.1 (soft tissue) and PCWG3 (bone) criteria. | From date of radomization to study completion(up to 3 years) | 
| Overall Survival (OS) | OS defined as time from randomization to death due to any cause. | From date of randomization to study completion (up to 4 years) | 
| Time to First Symptomatic Skeletal -Related Event (SSRE) | Time from randomization to first SSRE as defined by any of the following or a combination: Use of radiation therapy to prevent or relieve skeletal symptoms. Occurrence of new symptomatic pathological bone fractures (vertebral or non-vertebral, resulting from minimal or no trauma). Occurrence of spinal cord compression. Orthopedic surgical intervention for bone metastasis. | From date of randomization to study completion (up to 3years) | 
| Duration of Response (DoR) | Duration of response (DoR) will be defined as the time from the date of first documented confirmed response (by BICR using RECIST 1.1 and PCWG3) until date of documented progression (by BICR) or death in the absence of disease progression. | From date of radomization to study completion (up to 3 years) | 
| Time to Opiate Use for Cancer Pain | Time to opiate use is defined as the time from randomization to the date of opiate use for cancer-related pain in participants who have not received any opiates at baseline. | From date of radomization to study completion (up to 3 years) | 
| Prostate Specific Antigen 50 Response (PSA50 response) | Prostate Specific Antigen (PSA) response is defined as the proportion of participants achieving a ≥50% decrease in PSA from baseline to the lowest post-baseline PSA result, confirmed by a second consecutive PSA assessment at least 3 weeks later. | From date of baseline confirmed to study completion (up to 3 years) | 
| Second Progression or Death (PFS2) | Defined as the time from randomization to second progression by investigator assessment of radiological or clinical progression or death from any cause, whichever occurs first. | From date of randomization to study completion (up to 3 years) | 
| Number of adverse events | Percentage of patients with any adverse event (AE), adverse event (AE) leading to study drug discontinuation, adverse event (AE) leading to death, serious adverse event (SAE), adverse event (AE) related to study drug, serious adverse event (SAE) related to study drug | From the time of signature of informed consent throughout the treatment period (up to 4 years plus 30 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metastatic castration-resistant prostate cancer (mCRPC), BRCA1/2 mutations