Galahad: An Efficacy and Safety Study of Niraparib in Men With Metastatic Castration-Resistant Prostate Cancer and DNA-Repair Anomalies

• Sponsor: Janssen Research & Development, LLC (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02854436
• Collaborator: (none)
• Enrollment: 289
• Locations: 110
• Arm: 1
• Anticipated Duration (Months): 74
• Patients Per Site: 2.6
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the efficacy, safety, and pharmacokinetics of niraparib in men with metastatic castration-resistant prostate cancer (mCRPC) and deoxyribonucleic acid (DNA) repair anomalies.

Condition or Disease	Intervention/Treatment	Phase
Prostatic Neoplasms	Drug: Niraparib	Phase 2

Detailed Description

This is a multicenter and open-label (participants and researchers are aware of the treatment that participants are receiving) study that consists of 4 phases: a Prescreening Phase for biomarker evaluation only, a Screening Phase, a Treatment Phase (Cycle 1 Day 1 and will continue until the study drug is discontinued), a Follow-up Phase (every 3 months after end of treatment visit), and a Long-term Extension Phase (until participants no longer derive benefit from treatment or until further notification on different means of study treatment). Participants will be monitored for safety during the study period, and up to 30 days after the last dose of study drug.

Study Design

• Study Type: Interventional
• Actual Enrollment: 289 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Efficacy and Safety Study of Niraparib in Men With Metastatic Castration-Resistant Prostate Cancer and DNA-Repair Anomalies
• Actual Study Start Date: Aug 31, 2016
• Actual Primary Completion Date: Jan 26, 2021
• Anticipated Study Completion Date: Oct 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Niraparib Participants will receive 300 milligram (mg) niraparib (3 capsules*100 mg) orally once daily.	Drug: Niraparib; Participants will receive 300 mg niraparib (3 capsules*100 mg) orally once daily.; Other Names: JNJ-64091742

Outcome Measures

Primary Outcome Measures

1. Objective Response Rate (ORR) for Participants With Measurable Metastatic Castration-resistant Prostate Cancer (mCRPC) and Breast Cancer Gene (BRCA) Mutation [Up to 52 months]

   ORR defined as percentage of participants with BRCA DNA-repair anomalies and measurable disease whose best response is either complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and with no evidence of bone progression per Prostate Cancer Working Group 3 (PCWG3) criteria.

Secondary Outcome Measures

1. Objective Response Rate for Participants With Measurable Metastatic Castration-resistant Prostate Cancer (mCRPC) and Non-Breast Cancer Gene (BRCA) Mutation [Up to 52 months]

   ORR defined as percentage of participants with BRCA deoxyribonucleic acid (DNA)-repair anomalies and measurable disease whose best response is either CR or PR per RECIST 1.1 and with no evidence of bone progression per PCWG3 criteria.

2. Circulating Tumor Cells (CTC) Response Rate [At 8 weeks post-baseline]

   CTC response rate was defined as the percentage of participants with CTC equals to (=) 0 per 7.5 milliliter (mL) blood at 8 weeks post-baseline in participants with baseline CTC greater than (>) 0.

3. Overall Survival (OS) [Up to 52 months]

   OS is defined as time from enrollment to death from any cause.

4. Radiographic Progression-Free Survival (rPFS) [Up to 52 months]

   rPFS was defined as time from enrollment to radiographic progression or death from any cause, whichever occurred first. Radiographic progression was evaluated per RECIST 1.1 criteria for soft tissue disease and per PCWG3 criteria for bone disease.

5. Time to Radiographic Progression [Up to 52 months]

   Time to radiographic progression is defined as time from enrollment to radiographic progression or death due to disease progression, whichever occurs first. Disease progression is defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.

6. Time to Prostate-Specific Antigen (PSA) Progression [Up to 52 months]

   Time to PSA progression was defined as time from enrollment to the first date of documented PSA progression based on PCWG3 criteria. A participant was considered to have a PSA progression if the PSA level had a 25 percent (%) or greater increase from nadir and an absolute increase of 2 nanograms per milliliter (ng/mL) or more, which is confirmed by a second value obtained in 3 or more weeks.

7. Time to Symptomatic Skeletal Event (SSE) [Up to 52 months]

   Time to SSE was defined as the time from enrollment to first occurrence of one of the following symptomatic skeletal events: tumor-related spinal cord compression, radiation to bone to relieve skeletal symptoms, surgery to bone or need for tumor-related orthopedic surgical intervention, symptomatic or pathologic fracture.

8. Duration of Objective Response [Up to 52 months]

   Duration of objective response is defined as time from CR or PR to radiographic progression of disease, unequivocal clinical progression or death, whichever occurs first. Unequivocal clinical progression defined as one or more of following: 1) deterioration in Eastern Cooperative Oncology Group Performance Status (ECOG PS) to Grade 3 or higher; 2) need to initiate any of following because of tumor progression (even in absence of radiographic evidence of disease): alternative anticancer therapy for prostate cancer, radiation therapy, surgical interventions for complications due to tumor progression.

9. Number of Participants With Adverse Events (AEs) [Up to 52 months]

   An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study.

10. Number of Participants With Worst Toxicity Grades for Clinical Laboratory Tests Based on National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) [Up to 52 months]

    Number of participants with worst toxicity grades for clinical laboratory tests (chemistry and hematology) based on NCI-CTCAE were reported. The chemistry laboratory parameters were: alanine aminotransferase (ALT) increased, alkaline phosphatase increased, aspartate aminotransferase (AST) increased, blood bilirubin increased, creatinine increased, gamma glutamyl transferase (GGT) increased and the hematology parameters were: hemoglobin increased, lymphocyte count increased. Grading was done as: Grade 1 (=mild), Grade 2 (=moderate), Grade 3 (=severe) and Grade 4 (=potentially life-threatening).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically confirmed prostate cancer (mixed histology is acceptable, with the exception of the small cell pure phenotype, which is excluded)

• Received a taxane-based chemotherapy for the treatment of metastatic prostate cancer with evidence of disease progression on or after treatment, or discontinued from a taxane-based chemotherapy due to an adverse event

• Received a second-generation or later androgen receptor (AR)-targeted therapy (for example, abiraterone acetate plus prednisone, enzalutamide, apalutamide) for the treatment of metastatic prostate cancer with evidence of disease progression or non-metastatic castration-resistant prostate cancer with evidence of subsequent metastasis

• Biomarker-positive by at least one of the following criteria: (a) Biallelic deoxyribonucleic acid (DNA)-repair anomaly based on a sponsor validated blood or tissue assay; (b) Germline pathogenic Breast Cancer gene (BRCA) 1 or BRCA2 by any test (somatic local results must be confirmed as positive by the sponsor-validated assay before dosing)

• Progression of metastatic prostate cancer in the setting of castrate levels of testosterone or history of bilateral orchiectomy at study entry

Exclusion Criteria:

• Prior treatment with a poly (adenosine diphosphate [ADP] ribose) polymerase (PARP) inhibitor

• Prior platinum-based chemotherapy for the treatment of prostate cancer

• Known history or current diagnosis of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML)

• Symptomatic or impending cord compression

• Symptomatic brain metastases

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Tucson	Arizona	United States
2		Los Angeles	California	United States
3		Riverside	California	United States
4		Sacramento	California	United States
5		Aurora	Colorado	United States
6		Denver	Colorado	United States
7		Evanston	Illinois	United States
8		Danville	Kentucky	United States
9		Louisville	Kentucky	United States
10		New Orleans	Louisiana	United States
11		Boston	Massachusetts	United States
12		Detroit	Michigan	United States
13		Omaha	Nebraska	United States
14		New York	New York	United States
15		Durham	North Carolina	United States
16		Lancaster	Pennsylvania	United States
17		Philadelphia	Pennsylvania	United States
18		Myrtle Beach	South Carolina	United States
19		Houston	Texas	United States
20		Charlottesville	Virginia	United States
21		Fairfax	Virginia	United States
22		Seattle	Washington	United States
23		Madison	Wisconsin	United States
24		Camperdown		Australia
25		Darlinghurst		Australia
26		East Albury		Australia
27		Kurralta Park		Australia
28		Macquarie University		Australia
29		Melbourne		Australia
30		Murdoch		Australia
31		Port Macquarie		Australia
32		Randwick		Australia
33		Wahroonga		Australia
34		Aalst		Belgium
35		Brussel		Belgium
36		Charleroi		Belgium
37		Gent		Belgium
38		Haine-Saint-Paul, La Louviere		Belgium
39		Hasselt		Belgium
40		Kortrijk		Belgium
41		Liège		Belgium
42		Namur		Belgium
43		Ottignies		Belgium
44		Wilrijk		Belgium
45		Barretos		Brazil
46		Belo Horizonte		Brazil
47		Curitiba		Brazil
48		Fortaleza		Brazil
49		Ijuí		Brazil
50		Itajai		Brazil
51		Joinville		Brazil
52		Natal		Brazil
53		Salvador		Brazil
54		Sao Paulo		Brazil
55		Vancouver	British Columbia	Canada
56		Oshawa	Ontario	Canada
57		Toronto	Ontario	Canada
58		Montreal	Quebec	Canada
59		Quebec		Canada
60		Aarhus N.		Denmark
61		Copenhagen N		Denmark
62		Herlev		Denmark
63		Odense C		Denmark
64		Avignon Cedex 9		France
65		Besancon		France
66		Caen		France
67		Lyon		France
68		Nice Cedex 2		France
69		Paris		France
70		Reims		France
71		Strasbourg		France
72		Villejuif Cedex		France
73		Beer-Sheva		Israel
74		Haifa		Israel
75		Kfar Saba		Israel
76		Ramat Gan		Israel
77		Zrifin		Israel
78		Seoul		Korea, Republic of
79		Alkmaar		Netherlands
80		Amsterdam		Netherlands
81		Groningen		Netherlands
82		Maastricht		Netherlands
83		Rotterdam		Netherlands
84		Moscow		Russian Federation
85		Omsk		Russian Federation
86		Tomsk		Russian Federation
87		Barcelona		Spain
88		Córdoba		Spain
89		Madrid		Spain
90		Málaga		Spain
91		Pozuelo de Alarcon		Spain
92		Santander		Spain
93		Santiago de Compostela		Spain
94		Sevilla		Spain
95		Valencia		Spain
96		Göteborg		Sweden
97		Lund		Sweden
98		Stockholm		Sweden
99		Umeå		Sweden
100		Kaohsiung		Taiwan
101		Taichung		Taiwan
102		Tainan		Taiwan
103		Taipei		Taiwan
104		Taoyuan County		Taiwan
105		Blackburn		United Kingdom
106		Bristol		United Kingdom
107		Cardiff		United Kingdom
108		Exeter		United Kingdom
109		London		United Kingdom
110		Preston		United Kingdom

Sponsors and Collaborators

• Janssen Research & Development, LLC

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study Documents (Full-Text)

• Study Protocol - Jul 17, 2020
• Statistical Analysis Plan - Feb 22, 2021

More Information

Publications

None provided.

• Responsible Party: Janssen Research & Development, LLC
• ClinicalTrials.gov Identifier: NCT02854436
• Other Study ID Numbers: CR108208; 64091742PCR2001; 2016-002057-38
• First Posted: Aug 3, 2016
• Last Update Posted: Aug 4, 2022
• Last Verified: Aug 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Janssen Research & Development, LLC: Prostate cancer; CRPC; Metastatic castrate-resistant prostate cancer; Prostate neoplasm; Galahad; Niraparib; DNA anomalies; DNA defect; PARP inhibitor; PARPi
• Additional relevant MeSH terms: Prostatic Neoplasms; Congenital Abnormalities; Niraparib

Study Results

Participant Flow

Arm/Group Title	Niraparib
Arm/Group Description	Male participants who were over the age of 18 years with metastatic castration-resistant prostate cancer (mCRPC) and deoxyribonucleic acid (DNA) repair anomalies and who had received prior taxane-based chemotherapy and androgen receptor (AR)-targeted therapy received once daily oral dose of 300 milligrams (mg) niraparib capsules starting Day 1 until disease progression, unacceptable toxicity, death, or termination of the study by the sponsor (up to 52 months).
Period Title: Overall Study
STARTED	289
Intent to Treat Participants (Breast Cancer Gene [BRCA] and Non-BRCA Participants)	223
COMPLETED	0
NOT COMPLETED	289

Baseline Characteristics

Arm/Group Title	Niraparib
Arm/Group Description	Male participants who were over the age of 18 years with metastatic castration-resistant prostate cancer (mCRPC) and deoxyribonucleic acid (DNA) repair anomalies and who had received prior taxane-based chemotherapy and androgen receptor (AR)-targeted therapy received once daily oral dose of 300 milligrams (mg) niraparib capsules starting Day 1 until disease progression, unacceptable toxicity, death, or termination of the study by the sponsor (up to 52 months).
Overall Participants	289
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	68.8 (7.8)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	289 100%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	16 5.5%
Black or African American	9 3.1%
Native Hawaiian or Other Pacific Islander	0 0%
White	205 70.9%
More than one race	3 1%
Unknown or Not Reported	51 17.6%
Other	5 1.7%
Region of Enrollment (Count of Participants)
AUSTRALIA	31 10.7%
BELGIUM	18 6.2%
BRAZIL	12 4.2%
CANADA	21 7.3%
DENMARK	1 0.3%
FRANCE	48 16.6%
ISRAEL	6 2.1%
NETHERLANDS	6 2.1%
RUSSIAN FEDERATION	7 2.4%
SOUTH KOREA	5 1.7%
SPAIN	39 13.5%
SWEDEN	24 8.3%
TAIWAN	9 3.1%
UNITED KINGDOM	17 5.9%
UNITED STATES	45 15.6%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (ORR) for Participants With Measurable Metastatic Castration-resistant Prostate Cancer (mCRPC) and Breast Cancer Gene (BRCA) Mutation
Description	ORR defined as percentage of participants with BRCA DNA-repair anomalies and measurable disease whose best response is either complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and with no evidence of bone progression per Prostate Cancer Working Group 3 (PCWG3) criteria.
Time Frame	Up to 52 months

Outcome Measure Data

Analysis Population Description

Measurable intent to treat (ITT) population also referred to as efficacy analysis set included all participants who received at least 1 dose of study drug and have BRCA (biallelic or germline DNA-repair anomalies) and measurable disease at baseline.

Arm/Group Title	Niraparib
Arm/Group Description	Male participants who were over the age of 18 years with metastatic castration-resistant prostate cancer (mCRPC) and deoxyribonucleic acid (DNA) repair anomalies and who had received prior taxane-based chemotherapy and androgen receptor (AR)-targeted therapy received once daily oral dose of 300 milligrams (mg) niraparib capsules starting Day 1 until disease progression, unacceptable toxicity, death, or termination of the study by the sponsor (up to 52 months).
Measure Participants	76
Number (95% Confidence Interval) [percentage of participants]	34.2 11.8%

2. Secondary Outcome

Title	Objective Response Rate for Participants With Measurable Metastatic Castration-resistant Prostate Cancer (mCRPC) and Non-Breast Cancer Gene (BRCA) Mutation
Description	ORR defined as percentage of participants with BRCA deoxyribonucleic acid (DNA)-repair anomalies and measurable disease whose best response is either CR or PR per RECIST 1.1 and with no evidence of bone progression per PCWG3 criteria.
Time Frame	Up to 52 months

Outcome Measure Data

Analysis Population Description

Measurable ITT analysis set included all participants who received at least 1 dose of study drug and have non-BRCA (biallelic DNA-repair anomaly) and measurable disease at baseline.

Arm/Group Title	Niraparib
Arm/Group Description	Male participants who were over the age of 18 years with metastatic castration-resistant prostate cancer (mCRPC) and deoxyribonucleic acid (DNA) repair anomalies and who had received prior taxane-based chemotherapy and androgen receptor (AR)-targeted therapy received once daily oral dose of 300 milligrams (mg) niraparib capsules starting Day 1 until disease progression, unacceptable toxicity, death, or termination of the study by the sponsor (up to 52 months).
Measure Participants	47
Number (95% Confidence Interval) [percentage of participants]	10.6 3.7%

3. Secondary Outcome

Title	Circulating Tumor Cells (CTC) Response Rate
Description	CTC response rate was defined as the percentage of participants with CTC equals to (=) 0 per 7.5 milliliter (mL) blood at 8 weeks post-baseline in participants with baseline CTC greater than (>) 0.
Time Frame	At 8 weeks post-baseline

Outcome Measure Data

Analysis Population Description

ITT analysis set included all participants who received at least 1 dose of study drug. Here 'N' (number of participants analysed) specifies the participants with baseline CTC (per 7.5 mL blood) > 0. Here, 'n' (number analyzed) specifies the number of participants evaluated for specific categories.

Arm/Group Title	Niraparib
Arm/Group Description	Male participants who were over the age of 18 years with metastatic castration-resistant prostate cancer (mCRPC) and deoxyribonucleic acid (DNA) repair anomalies and who had received prior taxane-based chemotherapy and androgen receptor (AR)-targeted therapy received once daily oral dose of 300 milligrams (mg) niraparib capsules starting Day 1 until disease progression, unacceptable toxicity, death, or termination of the study by the sponsor (up to 52 months).
Measure Participants	202
BRCA	23.7 8.2%
Non-BRCA	8.5 2.9%

4. Secondary Outcome

Title	Overall Survival (OS)
Description	OS is defined as time from enrollment to death from any cause.
Time Frame	Up to 52 months

Outcome Measure Data

Analysis Population Description

ITT analysis set included participants who had received at least 1 dose of study drug. Here, 'n' (number analyzed) specifies the number of participants evaluated for specific categories.

Arm/Group Title	Niraparib
Arm/Group Description	Male participants who were over the age of 18 years with metastatic castration-resistant prostate cancer (mCRPC) and deoxyribonucleic acid (DNA) repair anomalies and who had received prior taxane-based chemotherapy and androgen receptor (AR)-targeted therapy received once daily oral dose of 300 milligrams (mg) niraparib capsules starting Day 1 until disease progression, unacceptable toxicity, death, or termination of the study by the sponsor (up to 52 months).
Measure Participants	223
BRCA	13.01
Non-BRCA	9.63

5. Secondary Outcome

Title	Radiographic Progression-Free Survival (rPFS)
Description	rPFS was defined as time from enrollment to radiographic progression or death from any cause, whichever occurred first. Radiographic progression was evaluated per RECIST 1.1 criteria for soft tissue disease and per PCWG3 criteria for bone disease.
Time Frame	Up to 52 months

Outcome Measure Data

Analysis Population Description

ITT analysis set included participants who had received at least 1 dose of study drug. Here, 'n' (number analyzed) specifies the number of participants evaluated for specific categories.

Arm/Group Title	Niraparib
Arm/Group Description	Male participants who were over the age of 18 years with metastatic castration-resistant prostate cancer (mCRPC) and deoxyribonucleic acid (DNA) repair anomalies and who had received prior taxane-based chemotherapy and androgen receptor (AR)-targeted therapy received once daily oral dose of 300 milligrams (mg) niraparib capsules starting Day 1 until disease progression, unacceptable toxicity, death, or termination of the study by the sponsor (up to 52 months).
Measure Participants	223
BRCA	8.08
Non-BRCA	3.71

6. Secondary Outcome

Title	Time to Radiographic Progression
Description	Time to radiographic progression is defined as time from enrollment to radiographic progression or death due to disease progression, whichever occurs first. Disease progression is defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.
Time Frame	Up to 52 months

Outcome Measure Data

Analysis Population Description

ITT analysis set included participants who had received at least 1 dose of study drug. Here, 'n' (number analyzed) specifies the number of participants evaluated for specific categories.

Arm/Group Title	Niraparib
Arm/Group Description	Male participants who were over the age of 18 years with metastatic castration-resistant prostate cancer (mCRPC) and deoxyribonucleic acid (DNA) repair anomalies and who had received prior taxane-based chemotherapy and androgen receptor (AR)-targeted therapy received once daily oral dose of 300 milligrams (mg) niraparib capsules starting Day 1 until disease progression, unacceptable toxicity, death, or termination of the study by the sponsor (up to 52 months).
Measure Participants	223
BRCA	8.08
Non-BRCA	3.78

7. Secondary Outcome

Title	Time to Prostate-Specific Antigen (PSA) Progression
Description	Time to PSA progression was defined as time from enrollment to the first date of documented PSA progression based on PCWG3 criteria. A participant was considered to have a PSA progression if the PSA level had a 25 percent (%) or greater increase from nadir and an absolute increase of 2 nanograms per milliliter (ng/mL) or more, which is confirmed by a second value obtained in 3 or more weeks.
Time Frame	Up to 52 months

Outcome Measure Data

Analysis Population Description

ITT analysis set included participants who had received at least 1 dose of study drug. Here, 'n' (number analyzed) specifies the number of participants evaluated for specific categories.

Arm/Group Title	Niraparib
Arm/Group Description	Male participants who were over the age of 18 years with metastatic castration-resistant prostate cancer (mCRPC) and deoxyribonucleic acid (DNA) repair anomalies and who had received prior taxane-based chemotherapy and androgen receptor (AR)-targeted therapy received once daily oral dose of 300 milligrams (mg) niraparib capsules starting Day 1 until disease progression, unacceptable toxicity, death, or termination of the study by the sponsor (up to 52 months).
Measure Participants	223
BRCA	5.13
Non-BRCA	3.65

8. Secondary Outcome

Title	Time to Symptomatic Skeletal Event (SSE)
Description	Time to SSE was defined as the time from enrollment to first occurrence of one of the following symptomatic skeletal events: tumor-related spinal cord compression, radiation to bone to relieve skeletal symptoms, surgery to bone or need for tumor-related orthopedic surgical intervention, symptomatic or pathologic fracture.
Time Frame	Up to 52 months

Outcome Measure Data

Analysis Population Description

ITT analysis set included participants who had received at least 1 dose of study drug. Here, 'n' (number analyzed) specifies the number of participants evaluated for specific categories.

Arm/Group Title	Niraparib
Arm/Group Description	Male participants who were over the age of 18 years with metastatic castration-resistant prostate cancer (mCRPC) and deoxyribonucleic acid (DNA) repair anomalies and who had received prior taxane-based chemotherapy and androgen receptor (AR)-targeted therapy received once daily oral dose of 300 milligrams (mg) niraparib capsules starting Day 1 until disease progression, unacceptable toxicity, death, or termination of the study by the sponsor (up to 52 months).
Measure Participants	223
BRCA	13.80
Non-BRCA	10.35

9. Secondary Outcome

Title	Duration of Objective Response
Description	Duration of objective response is defined as time from CR or PR to radiographic progression of disease, unequivocal clinical progression or death, whichever occurs first. Unequivocal clinical progression defined as one or more of following: 1) deterioration in Eastern Cooperative Oncology Group Performance Status (ECOG PS) to Grade 3 or higher; 2) need to initiate any of following because of tumor progression (even in absence of radiographic evidence of disease): alternative anticancer therapy for prostate cancer, radiation therapy, surgical interventions for complications due to tumor progression.
Time Frame	Up to 52 months

Outcome Measure Data

Analysis Population Description

Measurable ITT responder analysis set included all participants who received at least 1 dose of study drug, responded to it and have BRCA or non-BRCA and measurable disease at baseline. Here, 'n' (number analyzed) specifies the number of participants evaluated for specific categories.

Arm/Group Title	Niraparib
Arm/Group Description	Male participants who were over the age of 18 years with metastatic castration-resistant prostate cancer (mCRPC) and deoxyribonucleic acid (DNA) repair anomalies and who had received prior taxane-based chemotherapy and androgen receptor (AR)-targeted therapy received once daily oral dose of 300 milligrams (mg) niraparib capsules starting Day 1 until disease progression, unacceptable toxicity, death, or termination of the study by the sponsor (up to 52 months).
Measure Participants	31
BRCA	5.55
non-BRCA	5.16

10. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs)
Description	An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study.
Time Frame	Up to 52 months

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of study drug.

Arm/Group Title	Niraparib
Arm/Group Description	Male participants who were over the age of 18 years with metastatic castration-resistant prostate cancer (mCRPC) and deoxyribonucleic acid (DNA) repair anomalies and who had received prior taxane-based chemotherapy and androgen receptor (AR)-targeted therapy received once daily oral dose of 300 milligrams (mg) niraparib capsules starting Day 1 until disease progression, unacceptable toxicity, death, or termination of the study by the sponsor (up to 52 months).
Measure Participants	289
Count of Participants [Participants]	288 99.7%

11. Secondary Outcome

Title	Number of Participants With Worst Toxicity Grades for Clinical Laboratory Tests Based on National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE)
Description	Number of participants with worst toxicity grades for clinical laboratory tests (chemistry and hematology) based on NCI-CTCAE were reported. The chemistry laboratory parameters were: alanine aminotransferase (ALT) increased, alkaline phosphatase increased, aspartate aminotransferase (AST) increased, blood bilirubin increased, creatinine increased, gamma glutamyl transferase (GGT) increased and the hematology parameters were: hemoglobin increased, lymphocyte count increased. Grading was done as: Grade 1 (=mild), Grade 2 (=moderate), Grade 3 (=severe) and Grade 4 (=potentially life-threatening).
Time Frame	Up to 52 months

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of study drug and with at least one postbaseline assessment for the specific lab test within the time period. Here, 'n' (number analyzed) specifies the number of participants evaluated for specific categories.

Arm/Group Title	Niraparib
Arm/Group Description	Male participants who were over the age of 18 years with metastatic castration-resistant prostate cancer (mCRPC) and deoxyribonucleic acid (DNA) repair anomalies and who had received prior taxane-based chemotherapy and androgen receptor (AR)-targeted therapy received once daily oral dose of 300 milligrams (mg) niraparib capsules starting Day 1 until disease progression, unacceptable toxicity, death, or termination of the study by the sponsor (up to 52 months).
Measure Participants	283
ALT increased (Grade 1 or 2)	67 23.2%
ALT increased (Grade 3 or 4)	4 1.4%
Alkaline phosphatase increased (Grade 1 or 2)	102 35.3%
Alkaline phosphatase increased (Grade 3 or 4)	7 2.4%
AST increased (Grade 1 or 2)	70 24.2%
AST increased (Grade 3 or 4)	4 1.4%
Blood bilirubin increased (Grade 1 or 2)	9 3.1%
Blood bilirubin increased (Grade 3 or 4)	2 0.7%
Creatinine increased (Grade 1 or 2)	45 15.6%
Creatinine increased (Grade 3 or 4)	2 0.7%
GGT increased (Grade 1 or 2)	105 36.3%
GGT increased (Grade 3 or 4)	14 4.8%
Hemoglobin increased (Grade 1 or 2)	0 0%
Hemoglobin increased (Grade 3 or 4)	0 0%
Lymphocyte count increased (Grade 1 or 2)	2 0.7%
Lymphocyte count increased (Grade 3 or 4)	0 0%

Adverse Events

Time Frame	Up to 52 months
Adverse Event Reporting Description	Safety analysis set included all participants who received at least 1 dose of study drug.
Arm/Group Title	Niraparib
Arm/Group Description	Male participants who were over the age of 18 years with metastatic castration-resistant prostate cancer (mCRPC) and deoxyribonucleic acid (DNA) repair anomalies and who had received prior taxane-based chemotherapy and androgen receptor (AR)-targeted therapy received once daily oral dose of 300 milligrams (mg) niraparib capsules starting Day 1 until disease progression, unacceptable toxicity, death, or termination of the study by the sponsor (up to 52 months).
All Cause Mortality
	Niraparib
	Affected / at Risk (%)	# Events
Total	208/289 (72%)
Serious Adverse Events
	Niraparib
	Affected / at Risk (%)	# Events
Total	134/289 (46.4%)
Blood and lymphatic system disorders
Anaemia	13/289 (4.5%)
Febrile Neutropenia	2/289 (0.7%)
Leukopenia	1/289 (0.3%)
Neutropenia	1/289 (0.3%)
Thrombocytopenia	17/289 (5.9%)
Cardiac disorders
Atrial Fibrillation	1/289 (0.3%)
Cardiac Arrest	1/289 (0.3%)
Cardiac Failure	1/289 (0.3%)
Cardiac Failure Congestive	1/289 (0.3%)
Ventricular Tachycardia	1/289 (0.3%)
Gastrointestinal disorders
Abdominal Pain	4/289 (1.4%)
Acute Abdomen	1/289 (0.3%)
Ascites	1/289 (0.3%)
Constipation	5/289 (1.7%)
Diarrhoea	2/289 (0.7%)
Gastritis	2/289 (0.7%)
Gastrointestinal Haemorrhage	1/289 (0.3%)
Inflammatory Bowel Disease	1/289 (0.3%)
Lower Gastrointestinal Haemorrhage	1/289 (0.3%)
Nausea	5/289 (1.7%)
Rectal Haemorrhage	1/289 (0.3%)
Small Intestinal Obstruction	1/289 (0.3%)
Stomatitis	2/289 (0.7%)
Volvulus	1/289 (0.3%)
Vomiting	7/289 (2.4%)
General disorders
Asthenia	4/289 (1.4%)
Facial Pain	1/289 (0.3%)
Fatigue	4/289 (1.4%)
General Physical Health Deterioration	8/289 (2.8%)
Non-Cardiac Chest Pain	1/289 (0.3%)
Pain	2/289 (0.7%)
Performance Status Decreased	1/289 (0.3%)
Pyrexia	4/289 (1.4%)
Systemic Inflammatory Response Syndrome	1/289 (0.3%)
Infections and infestations
Abdominal Infection	1/289 (0.3%)
Abscess Jaw	1/289 (0.3%)
Cellulitis	1/289 (0.3%)
Escherichia Urinary Tract Infection	2/289 (0.7%)
Herpes Zoster	1/289 (0.3%)
Infected Lymphocele	1/289 (0.3%)
Infection	1/289 (0.3%)
Lower Respiratory Tract Infection	1/289 (0.3%)
Malaria	1/289 (0.3%)
Neutropenic Sepsis	1/289 (0.3%)
Osteomyelitis	2/289 (0.7%)
Pneumocystis Jirovecii Pneumonia	1/289 (0.3%)
Pneumonia	4/289 (1.4%)
Pneumonia Haemophilus	1/289 (0.3%)
Pyelonephritis Acute	2/289 (0.7%)
Sepsis	5/289 (1.7%)
Septic Shock	2/289 (0.7%)
Skin Infection	1/289 (0.3%)
Spinal Cord Infection	1/289 (0.3%)
Urinary Tract Infection	3/289 (1%)
Urosepsis	2/289 (0.7%)
Injury, poisoning and procedural complications
Cystitis Radiation	1/289 (0.3%)
Extradural Haematoma	1/289 (0.3%)
Femur Fracture	1/289 (0.3%)
Head Injury	1/289 (0.3%)
Hip Fracture	2/289 (0.7%)
Spinal Fracture	1/289 (0.3%)
Investigations
Blood Calcium Increased	1/289 (0.3%)
Blood Creatinine Increased	1/289 (0.3%)
Electrocardiogram QT Prolonged	1/289 (0.3%)
Metabolism and nutrition disorders
Dehydration	4/289 (1.4%)
Hypercalcaemia	1/289 (0.3%)
Hypocalcaemia	1/289 (0.3%)
Hypokalaemia	1/289 (0.3%)
Hyponatraemia	2/289 (0.7%)
Hypophosphataemia	1/289 (0.3%)
Hypovolaemia	1/289 (0.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	3/289 (1%)
Back Pain	7/289 (2.4%)
Bone Pain	3/289 (1%)
Joint Effusion	1/289 (0.3%)
Muscular Weakness	3/289 (1%)
Musculoskeletal Pain	1/289 (0.3%)
Myalgia	1/289 (0.3%)
Pain in Extremity	1/289 (0.3%)
Pain in Jaw	1/289 (0.3%)
Pathological Fracture	1/289 (0.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal Cell Carcinoma	1/289 (0.3%)
Gastrointestinal Stromal Tumour	1/289 (0.3%)
Metastases to Meninges	3/289 (1%)
Prostate Cancer Metastatic	2/289 (0.7%)
Tumour Pain	1/289 (0.3%)
Nervous system disorders
Altered State of Consciousness	1/289 (0.3%)
Cauda Equina Syndrome	1/289 (0.3%)
Cerebrovascular Accident	1/289 (0.3%)
Headache	6/289 (2.1%)
Ischaemic Stroke	2/289 (0.7%)
Monoparesis	1/289 (0.3%)
Nerve Compression	1/289 (0.3%)
Neuropathy Peripheral	1/289 (0.3%)
Paraparesis	1/289 (0.3%)
Presyncope	1/289 (0.3%)
Spinal Cord Compression	6/289 (2.1%)
Syncope	2/289 (0.7%)
Transient Ischaemic Attack	1/289 (0.3%)
Psychiatric disorders
Confusional State	2/289 (0.7%)
Renal and urinary disorders
Acute Kidney Injury	2/289 (0.7%)
Haematuria	6/289 (2.1%)
Renal Impairment	1/289 (0.3%)
Urinary Retention	2/289 (0.7%)
Reproductive system and breast disorders
Prostatitis	1/289 (0.3%)
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Failure	1/289 (0.3%)
Chronic Obstructive Pulmonary Disease	1/289 (0.3%)
Dyspnoea	1/289 (0.3%)
Lung Disorder	1/289 (0.3%)
Pneumonitis	1/289 (0.3%)
Pulmonary Embolism	1/289 (0.3%)
Respiratory Distress	1/289 (0.3%)
Vascular disorders
Deep Vein Thrombosis	1/289 (0.3%)
Embolism	1/289 (0.3%)
Hypotension	2/289 (0.7%)
Phlebitis	1/289 (0.3%)
Other (Not Including Serious) Adverse Events
	Niraparib
	Affected / at Risk (%)	# Events
Total	280/289 (96.9%)
Blood and lymphatic system disorders
Anaemia	154/289 (53.3%)
Leukopenia	27/289 (9.3%)
Lymphopenia	24/289 (8.3%)
Neutropenia	54/289 (18.7%)
Thrombocytopenia	94/289 (32.5%)
Gastrointestinal disorders
Abdominal Pain	23/289 (8%)
Constipation	98/289 (33.9%)
Diarrhoea	48/289 (16.6%)
Dry Mouth	20/289 (6.9%)
Dyspepsia	21/289 (7.3%)
Nausea	167/289 (57.8%)
Stomatitis	19/289 (6.6%)
Vomiting	109/289 (37.7%)
General disorders
Asthenia	45/289 (15.6%)
Fatigue	105/289 (36.3%)
Oedema Peripheral	41/289 (14.2%)
Pyrexia	17/289 (5.9%)
Investigations
Alanine Aminotransferase Increased	17/289 (5.9%)
Aspartate Aminotransferase Increased	20/289 (6.9%)
Blood Alkaline Phosphatase Increased	26/289 (9%)
Electrocardiogram QT Prolonged	17/289 (5.9%)
Gamma-Glutamyltransferase Increased	25/289 (8.7%)
Weight Decreased	50/289 (17.3%)
Metabolism and nutrition disorders
Decreased Appetite	93/289 (32.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	43/289 (14.9%)
Back Pain	59/289 (20.4%)
Bone Pain	30/289 (10.4%)
Musculoskeletal Pain	29/289 (10%)
Pain in Extremity	30/289 (10.4%)
Nervous system disorders
Dizziness	19/289 (6.6%)
Dysgeusia	17/289 (5.9%)
Headache	30/289 (10.4%)
Psychiatric disorders
Insomnia	24/289 (8.3%)
Respiratory, thoracic and mediastinal disorders
Cough	17/289 (5.9%)
Dyspnoea	39/289 (13.5%)
Vascular disorders
Hot Flush	17/289 (5.9%)
Hypertension	34/289 (11.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.