Back to resultsClinical 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
Primary Purpose
Metastatic Castration-resistant Prostate Cancer
Status
Recruiting
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
olaparib
enzalutamide
abiraterone acetate
Prednisone
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Castration-resistant Prostate Cancer focused on measuring metastatic castration-resistant prostate cancer (mCRPC), BRCA1/2 mutations
Eligibility Criteria
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.
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Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Olaparib
Enzalutamide OR abiraterone acetate
Arm Description
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
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Overall Survival (OS)
OS defined as time from randomization to death due to any cause.
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.
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.
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.
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.
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.
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
Full Information
NCT ID
NCT05457257
First Posted
July 11, 2022
Last Updated
October 2, 2023
Sponsor
AstraZeneca
Collaborators
Merck Sharp & Dohme LLC, Foundation Medicine, Inc., Myriad Genetics, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT05457257
Brief Title
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
Official Title
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)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 29, 2022 (Actual)
Primary Completion Date
June 28, 2024 (Anticipated)
Study Completion Date
September 30, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
Collaborators
Merck Sharp & Dohme LLC, Foundation Medicine, Inc., Myriad Genetics, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Castration-resistant Prostate Cancer
Keywords
metastatic castration-resistant prostate cancer (mCRPC), BRCA1/2 mutations
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
42 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Olaparib
Arm Type
Experimental
Arm Description
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
Arm Title
Enzalutamide OR abiraterone acetate
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
olaparib
Other Intervention Name(s)
Lynparza
Intervention Description
300 mg (2x 150 mg tablets) twice daily
Intervention Type
Drug
Intervention Name(s)
enzalutamide
Other Intervention Name(s)
XTANDI
Intervention Description
160 mg (4 x 40 mg capsules) once daily
Intervention Type
Drug
Intervention Name(s)
abiraterone acetate
Other Intervention Name(s)
ZYTIGA
Intervention Description
1,000 mg (4 x 250 mg tablets) once daily
Intervention Type
Drug
Intervention Name(s)
Prednisone
Intervention Description
5mg(5mg x 1 tablet) twice daily
Primary Outcome Measure Information:
Title
Radiological progression free survival (rPFS)
Description
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.
Time Frame
From date of randomization to study completion (up to 3 years)
Secondary Outcome Measure Information:
Title
Confirmed Objective Response Rate (ORR)
Description
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.
Time Frame
From date of radomization to study completion(up to 3 years)
Title
Overall Survival (OS)
Description
OS defined as time from randomization to death due to any cause.
Time Frame
From date of randomization to study completion (up to 4 years)
Title
Time to First Symptomatic Skeletal -Related Event (SSRE)
Description
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.
Time Frame
From date of randomization to study completion (up to 3years)
Title
Duration of Response (DoR)
Description
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.
Time Frame
From date of radomization to study completion (up to 3 years)
Title
Time to Opiate Use for Cancer Pain
Description
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.
Time Frame
From date of radomization to study completion (up to 3 years)
Title
Prostate Specific Antigen 50 Response (PSA50 response)
Description
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.
Time Frame
From date of baseline confirmed to study completion (up to 3 years)
Title
Second Progression or Death (PFS2)
Description
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.
Time Frame
From date of randomization to study completion (up to 3 years)
Title
Number of adverse events
Description
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
Time Frame
From the time of signature of informed consent throughout the treatment period (up to 4 years plus 30 days)
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
AstraZeneca Clinical Study Information Center
Phone
1-877-240-9479
Email
information.center@astrazeneca.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Fangjian Zhou, M.D.
Organizational Affiliation
Sun Yat-sen University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Research Site
City
Beijing
ZIP/Postal Code
100050
Country
China
Individual Site Status
Recruiting
Facility Name
Research Site
City
Bengbu
ZIP/Postal Code
233060
Country
China
Individual Site Status
Recruiting
Facility Name
Research Site
City
Changsha
ZIP/Postal Code
410008
Country
China
Individual Site Status
Recruiting
Facility Name
Research Site
City
Changsha
ZIP/Postal Code
410013
Country
China
Individual Site Status
Recruiting
Facility Name
Research Site
City
Chengdu
ZIP/Postal Code
610000
Country
China
Individual Site Status
Recruiting
Facility Name
Research Site
City
Chongqing
ZIP/Postal Code
400030
Country
China
Individual Site Status
Withdrawn
Facility Name
Research Site
City
Chongqing
Country
China
Individual Site Status
Recruiting
Facility Name
Research Site
City
Fuzhou
ZIP/Postal Code
350005
Country
China
Individual Site Status
Recruiting
Facility Name
Research Site
City
Guangzhou
ZIP/Postal Code
510060
Country
China
Individual Site Status
Recruiting
Facility Name
Research Site
City
Guangzhou
ZIP/Postal Code
510180
Country
China
Individual Site Status
Recruiting
Facility Name
Research Site
City
Guiyang
ZIP/Postal Code
550002
Country
China
Individual Site Status
Withdrawn
Facility Name
Research Site
City
Hangzhou
ZIP/Postal Code
310003
Country
China
Individual Site Status
Recruiting
Facility Name
Research Site
City
Hangzhou
ZIP/Postal Code
310009
Country
China
Individual Site Status
Recruiting
Facility Name
Research Site
City
Hangzhou
ZIP/Postal Code
310014
Country
China
Individual Site Status
Recruiting
Facility Name
Research Site
City
Hankou,Wuhan
ZIP/Postal Code
430022
Country
China
Individual Site Status
Recruiting
Facility Name
Research Site
City
Hefei
ZIP/Postal Code
230601
Country
China
Individual Site Status
Recruiting
Facility Name
Research Site
City
Jiaxing
ZIP/Postal Code
314001
Country
China
Individual Site Status
Recruiting
Facility Name
Research Site
City
Jinan
ZIP/Postal Code
250012
Country
China
Individual Site Status
Recruiting
Facility Name
Research Site
City
Jinan
ZIP/Postal Code
250021
Country
China
Individual Site Status
Recruiting
Facility Name
Research Site
City
Jining
ZIP/Postal Code
272029
Country
China
Individual Site Status
Recruiting
Facility Name
Research Site
City
Kunming
ZIP/Postal Code
650101
Country
China
Individual Site Status
Recruiting
Facility Name
Research Site
City
Lanzhou
ZIP/Postal Code
730030
Country
China
Individual Site Status
Recruiting
Facility Name
Research Site
City
Linyi
ZIP/Postal Code
276000
Country
China
Individual Site Status
Recruiting
Facility Name
Research Site
City
Nanchang
ZIP/Postal Code
330006
Country
China
Individual Site Status
Recruiting
Facility Name
Research Site
City
Nantong
ZIP/Postal Code
226361
Country
China
Individual Site Status
Recruiting
Facility Name
Research Site
City
Ningbo
ZIP/Postal Code
315010
Country
China
Individual Site Status
Recruiting
Facility Name
Research Site
City
Shanghai
ZIP/Postal Code
200002
Country
China
Individual Site Status
Recruiting
Facility Name
Research Site
City
Shanghai
ZIP/Postal Code
200032
Country
China
Individual Site Status
Recruiting
Facility Name
Research Site
City
Shenyang
ZIP/Postal Code
110004
Country
China
Individual Site Status
Recruiting
Facility Name
Research Site
City
Suzhou
ZIP/Postal Code
215004
Country
China
Individual Site Status
Recruiting
Facility Name
Research Site
City
Taiyuan
ZIP/Postal Code
030000
Country
China
Individual Site Status
Recruiting
Facility Name
Research Site
City
Tianjin
ZIP/Postal Code
300060
Country
China
Individual Site Status
Recruiting
Facility Name
Research Site
City
Wanzhou
ZIP/Postal Code
404000
Country
China
Individual Site Status
Recruiting
Facility Name
Research Site
City
Wuxi
ZIP/Postal Code
214001
Country
China
Individual Site Status
Recruiting
Facility Name
Research Site
City
Wuxi
ZIP/Postal Code
214023
Country
China
Individual Site Status
Recruiting
Facility Name
Research Site
City
XI 'an
ZIP/Postal Code
710077
Country
China
Individual Site Status
Recruiting
Facility Name
Research Site
City
Zhengzhou
Country
China
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment（https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure).
"Yes" indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
IPD Sharing Time Frame
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
IPD Sharing Access Criteria
When a request has been approved, AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access.For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
IPD Sharing URL
https://astrazenecagroup-dt.pharmacm.com/DT/Home
Learn more about this trial
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
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