Clinical Trials List
Protocol Number64091742PCR2001
NCT Number(ClinicalTrials.gov Identfier)NCT02854436
Completed
2017-06-01 - 2021-01-06
Phase II
Terminated7
ICD-10C61
Malignant neoplasm of prostate
A Phase 2 Efficacy and Safety Study of Niraparib in Men With Metastatic Castration-Resistant Prostate Cancer and DNA-Repair Anomalies
-
Trial Applicant
Johnson & Johnson
-
Sponsor
Janssen Research & Development, LLC
-
Trial scale
Multi-Regional Multi-Center
-
Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- Chi-Ping Huang Division of Urology
- Che-Hung Lin Division of Hematology & Oncology
- Po-Jen Hsiao 無
- Chao-Hsiang Chang Division of Urology
- Su-Peng Yeh Division of Hematology & Oncology
- Chi-Rei Yang Division of Urology
- 陳冠亨 Division of Urology
- Wei-Ching Lin Division of Radiology
- Po-Fan Hsieh Division of Urology
- Yi-Huei Chang Division of Urology
- Ching-Chan Lin Division of Urology
- 謝德鈞 Division of Nuclear Medicine
The Actual Total Number of Participants Enrolled
0 Completed
Co-Principal Investigator
- Chia-Yen Lin Division of Urology
- 王樹吉 Division of Urology
- 熊小澐 Division of Radiology
- Chuan-Shu Chen Division of Urology
- 蔡世傳 Division of Nuclear Medicine
- Cheng-Kuang Yang Division of Urology
- 洪晟鈞 Division of Urology
- Jian-Ri Li Division of Urology
- 裘坤元 Division of Urology
- 盧嘉文 Division of Urology
- Cheng-Che Chen Division of Urology
The Actual Total Number of Participants Enrolled
0 Completed
Co-Principal Investigator
- Yeong-Shiau Pu Division of Urology
- Ying-Chun Shen Division of Hematology & Oncology
- Yu-Chieh Tsai Division of Hematology & Oncology
- JHE-CYUAN GUO Division of Hematology & Oncology
- - - Division of Urology
- CHING-CHU LU Division of Nuclear Medicine
- CHUNG-HSIN CHEN Division of Urology
- YEN-HENG LIN Division of Radiology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- 盧凱傑 Division of Hematology & Oncology
- Rita cheng Division of Hematology & Oncology
- Po-Jung Su Division of Hematology & Oncology
- Yung-Chang Lin Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Jiann-Hui Ou Division of Hematology & Oncology
- Che-Yuan Hu Division of Hematology & Oncology
- 姜乃榕 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Condition/Disease
Metastatic Castration-Resistant Prostate Cancer
Objectives
Primary
To assess the efficacy of niraparib in subjects with measurable mCRPC and DNA-repair anomalies
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.
Test Drug
Niraparib
Active Ingredient
Niraparib
Dosage Form
capsule
Dosage
100
Endpoints
Primary Outcome Measures :
Objective Response Rate (ORR) [ Time Frame: Screening, Cycle 1 (each cycle of 28 days) Day 1 (every 8 weeks for the first 6 months and then every 12 weeks thereafter) till Follow-up Phase ]
ORR of soft tissue disease with no evidence of bone progression in participants with either biallelic Breast Cancer gene 1 (BRCA1) or Breast Cancer gene 2 (BRCA2) or germline BRCA. ORR in participants with measurable metastatic castration-resistant prostate cancer (mCRPC) and DNA-repair anomalies. ORR of soft tissue (visceral or nodal disease) as defined by RECIST 1.1 with no evidence of bone progression according to the Prostate Cancer Working Group 3 (PCWG3) criteria.
Secondary Outcome Measures :
Objective Response Rate (ORR) [ Time Frame: Up to 4 years and 6 months ]
ORR in participants with measurable metastatic castration-resistant prostate cancer (mCRPC) and DNA-repair anomalies. ORR of soft tissue (visceral or nodal disease) as defined by RECIST 1.1 with no evidence of bone progression according to the Prostate Cancer Working Group 3 (PCWG3) criteria.
Circulating Tumor Cells (CTC) Response [ Time Frame: From Screening till End of Treatment (30 {+/- 5} days of last dose -up to 4 years and 6 months) ]
CTC response defined as CTC=0 per 7.5 milliliter (mL) blood at 8 weeks post-baseline in participants with baseline CTC greater than (>) 0.
Overall Survival (OS) [ Time Frame: From enrollment to completion of study (up to 4 years and 6 months) ]
OS is defined as time from enrollment to death from any cause.
Radiographic Progression-Free Survival (rPFS) [ Time Frame: From enrollment to completion of study (up to 4 years and 6 months) ]
rPFS is defined as time from enrollment to radiographic progression or death.
Time to Prostate Specific Antigen (PSA) Progression [ Time Frame: From enrollment to completion of study (up to 4 years and 6 months) ]
First PSA increase that is 25 percent (%) or greater and an absolute increase of 2 nanogram/milliliter (ng/mL) or more above the nadir.
Time to Symptomatic Skeletal Event (SSE) [ Time Frame: From enrollment to completion of study (up to 4 years and 6 months) ]
Time to SSE: time from enrollment to first symptomatic fracture, radiation or surgery to bone, or spinal cord compression.
Number of Participants With Adverse Events as a Measure of Safety and Tolerability [ Time Frame: From enrollment to completion of study (up to 4 years and 6 months) ]
Duration of Objective Response [ Time Frame: From complete response (CR) or partial response (PR) to radiographic progression of disease (up to 4 years 6 months) ]
Duration of objective response is defined as time from complete response or partial response to radiographic progression of disease, unequivocal clinical progression or death, whichever occurs first.
Objective Response Rate (ORR) [ Time Frame: Screening, Cycle 1 (each cycle of 28 days) Day 1 (every 8 weeks for the first 6 months and then every 12 weeks thereafter) till Follow-up Phase ]
ORR of soft tissue disease with no evidence of bone progression in participants with either biallelic Breast Cancer gene 1 (BRCA1) or Breast Cancer gene 2 (BRCA2) or germline BRCA. ORR in participants with measurable metastatic castration-resistant prostate cancer (mCRPC) and DNA-repair anomalies. ORR of soft tissue (visceral or nodal disease) as defined by RECIST 1.1 with no evidence of bone progression according to the Prostate Cancer Working Group 3 (PCWG3) criteria.
Secondary Outcome Measures :
Objective Response Rate (ORR) [ Time Frame: Up to 4 years and 6 months ]
ORR in participants with measurable metastatic castration-resistant prostate cancer (mCRPC) and DNA-repair anomalies. ORR of soft tissue (visceral or nodal disease) as defined by RECIST 1.1 with no evidence of bone progression according to the Prostate Cancer Working Group 3 (PCWG3) criteria.
Circulating Tumor Cells (CTC) Response [ Time Frame: From Screening till End of Treatment (30 {+/- 5} days of last dose -up to 4 years and 6 months) ]
CTC response defined as CTC=0 per 7.5 milliliter (mL) blood at 8 weeks post-baseline in participants with baseline CTC greater than (>) 0.
Overall Survival (OS) [ Time Frame: From enrollment to completion of study (up to 4 years and 6 months) ]
OS is defined as time from enrollment to death from any cause.
Radiographic Progression-Free Survival (rPFS) [ Time Frame: From enrollment to completion of study (up to 4 years and 6 months) ]
rPFS is defined as time from enrollment to radiographic progression or death.
Time to Prostate Specific Antigen (PSA) Progression [ Time Frame: From enrollment to completion of study (up to 4 years and 6 months) ]
First PSA increase that is 25 percent (%) or greater and an absolute increase of 2 nanogram/milliliter (ng/mL) or more above the nadir.
Time to Symptomatic Skeletal Event (SSE) [ Time Frame: From enrollment to completion of study (up to 4 years and 6 months) ]
Time to SSE: time from enrollment to first symptomatic fracture, radiation or surgery to bone, or spinal cord compression.
Number of Participants With Adverse Events as a Measure of Safety and Tolerability [ Time Frame: From enrollment to completion of study (up to 4 years and 6 months) ]
Duration of Objective Response [ Time Frame: From complete response (CR) or partial response (PR) to radiographic progression of disease (up to 4 years 6 months) ]
Duration of objective response is defined as time from complete response or partial response to radiographic progression of disease, unequivocal clinical progression or death, whichever occurs first.
Inclution Criteria
Inclusion Criteria
1. Male
2. >18 years of age (or the legal age of consent in the jurisdiction in which the study is
taking place).
3. Signed main study ICF indicating that the subject understands the purpose of, and
procedures required for, the study and is willing to participate in the study.
4. Criterion modified per Amendment 2.
4.1. Histologically confirmed prostate cancer (mixed histology is acceptable, with the
exception of the small cell pure phenotype, which is be excluded).
5. Criterion modified per Amendment 2.
5.1. Documented evidence of disease progression while on treatment with at least 1
taxane-based chemotherapy for prostate cancer.
6. Criterion modified per Amendment 2.
6.1. Documented evidence of disease progression while on treatment with at least 1
AR-targeted therapy (eg, abiraterone acetate, enzalutamide, apalutamide) for prostate
cancer.
7. Tumor that is biomarker-positive for DNA-repair anomalies (See Section 9.7).
8. Criterion modified per Amendment 2.
8.1. Progression of metastatic prostate cancer in the setting of castrate levels of
testosterone ≤50 ng/dL on a gonadotropin releasing hormone analog (GnRHa), or
history of bilateral orchiectomy at study entry defined as having one or more of the
following:
a. PSA progression defined by a minimum of 2 rising PSA levels with an interval
of ≥1 week between each determination (per Prostate Cancer Working Group 3
[PCWG3] criteria).18 The PSA level at the screening visit should be ≥2 μg/L
(2 ng/mL).
b. Radiographic progression of soft tissue by RECIST 1.1 or bone disease by
PCWG3 criteria18 as defined below:
I. Soft tissue disease (measurable) by RECIST 1.1 defined as having
one or more of the following:
i. Nodal disease (pelvic or extrapelvic [retroperitoneal,
mediastinal, thoracic, other]) with lesions ≥1.5 cm in the
short axis.
ii. Visceral disease (lung, liver, adrenal) with lesions ≥1 cm in
the long axis.
II. Bone disease (non-measurable) defined as having bone lesions in the absence of measurable soft tissue disease.
9. Must be able to continue GnRHa during the course of the study if not surgically castrate.
10. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of ≤2 (see
Attachment 3).
11. Must be able to swallow whole capsules.
12. Subject must agree to use medically accepted and highly effective methods of
contraception during the course of the study and for 3 months after the last dose of study
drug.
13. To avoid risk of drug exposure through the ejaculate (even men with vasectomies),
subjects must agree while on study drug and for 3 months following the last dose of
study drug to:
a. Use a condom during sexual activity.
b. Not donate sperm.
14. Criterion modified per Amendment 2.
14.1. At screening, the following laboratory parameters must be met:
a. Absolute neutrophil count (ANC) ≥1.5 x 109
/L
b. Hemoglobin ≥9.0 g/dL
c. Platelet count ≥100 x 109
/L
d. Serum albumin ≥3 g/dL
e. Serum creatinine ≤1.5 x upper limit of normal (ULN), or a calculated
creatinine clearance ≥60 mL/min using the Cockcroft-Gault equation
f. Serum potassium ≥3.5 mmol/L
g. Serum total bilirubin ≤1.5 × ULN or direct bilirubin ≤1 x ULN (Note: in
subjects with Gilbert’s syndrome, if total bilirubin is >1.5 x ULN, measure
direct and indirect bilirubin, and if direct bilirubin is ≤1.5 x ULN, subject may
be eligible)
h. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT)
≤3.0 x ULN or ≤5 x ULN in the presence of liver metastases
i. CTC count of ≥1 cells/7.5 mL blood
1. Male
2. >18 years of age (or the legal age of consent in the jurisdiction in which the study is
taking place).
3. Signed main study ICF indicating that the subject understands the purpose of, and
procedures required for, the study and is willing to participate in the study.
4. Criterion modified per Amendment 2.
4.1. Histologically confirmed prostate cancer (mixed histology is acceptable, with the
exception of the small cell pure phenotype, which is be excluded).
5. Criterion modified per Amendment 2.
5.1. Documented evidence of disease progression while on treatment with at least 1
taxane-based chemotherapy for prostate cancer.
6. Criterion modified per Amendment 2.
6.1. Documented evidence of disease progression while on treatment with at least 1
AR-targeted therapy (eg, abiraterone acetate, enzalutamide, apalutamide) for prostate
cancer.
7. Tumor that is biomarker-positive for DNA-repair anomalies (See Section 9.7).
8. Criterion modified per Amendment 2.
8.1. Progression of metastatic prostate cancer in the setting of castrate levels of
testosterone ≤50 ng/dL on a gonadotropin releasing hormone analog (GnRHa), or
history of bilateral orchiectomy at study entry defined as having one or more of the
following:
a. PSA progression defined by a minimum of 2 rising PSA levels with an interval
of ≥1 week between each determination (per Prostate Cancer Working Group 3
[PCWG3] criteria).18 The PSA level at the screening visit should be ≥2 μg/L
(2 ng/mL).
b. Radiographic progression of soft tissue by RECIST 1.1 or bone disease by
PCWG3 criteria18 as defined below:
I. Soft tissue disease (measurable) by RECIST 1.1 defined as having
one or more of the following:
i. Nodal disease (pelvic or extrapelvic [retroperitoneal,
mediastinal, thoracic, other]) with lesions ≥1.5 cm in the
short axis.
ii. Visceral disease (lung, liver, adrenal) with lesions ≥1 cm in
the long axis.
II. Bone disease (non-measurable) defined as having bone lesions in the absence of measurable soft tissue disease.
9. Must be able to continue GnRHa during the course of the study if not surgically castrate.
10. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of ≤2 (see
Attachment 3).
11. Must be able to swallow whole capsules.
12. Subject must agree to use medically accepted and highly effective methods of
contraception during the course of the study and for 3 months after the last dose of study
drug.
13. To avoid risk of drug exposure through the ejaculate (even men with vasectomies),
subjects must agree while on study drug and for 3 months following the last dose of
study drug to:
a. Use a condom during sexual activity.
b. Not donate sperm.
14. Criterion modified per Amendment 2.
14.1. At screening, the following laboratory parameters must be met:
a. Absolute neutrophil count (ANC) ≥1.5 x 109
/L
b. Hemoglobin ≥9.0 g/dL
c. Platelet count ≥100 x 109
/L
d. Serum albumin ≥3 g/dL
e. Serum creatinine ≤1.5 x upper limit of normal (ULN), or a calculated
creatinine clearance ≥60 mL/min using the Cockcroft-Gault equation
f. Serum potassium ≥3.5 mmol/L
g. Serum total bilirubin ≤1.5 × ULN or direct bilirubin ≤1 x ULN (Note: in
subjects with Gilbert’s syndrome, if total bilirubin is >1.5 x ULN, measure
direct and indirect bilirubin, and if direct bilirubin is ≤1.5 x ULN, subject may
be eligible)
h. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT)
≤3.0 x ULN or ≤5 x ULN in the presence of liver metastases
i. CTC count of ≥1 cells/7.5 mL blood
Exclusion Criteria
Exclusion Criteria
1. Prior treatment with a PARP inhibitor.
2. Criterion modified per Amendment 2.
2.1. Prior platinum-based chemotherapy for the treatment of prostate cancer.
3. Known history or current diagnosis of myelodysplastic syndrome (MDS)/acute myeloid
leukemia (AML).
4. Known symptomatic or impending cord compression, except if subject has received
definitive treatment for this and demonstrates evidence of clinically stable disease.
5. Known symptomatic uncontrolled brain or leptomeningeal metastases (controlled is
defined as CNS disease which has undergone treatment [eg, radiation or surgery] at
least 15 days prior to Cycle 1 Day 1).
6. Known allergies, hypersensitivity, or intolerance to niraparib or its excipients (refer to
Investigator's Brochure).12
7. Any condition for which, in the opinion of the investigator, participation would not be
in the best interest of the subject (eg, compromise the well-being) or that could prevent,
limit, or confound the protocol-specified assessments.
8. Known disorder affecting gastrointestinal absorption.
9. Active cancer (other than prostate cancer; or basal cell or squamous cell skin cancer,
non-muscle invasive bladder cancer [stages pTaG1 and pTaG2], or any other cancer in
situ currently in complete remission) within 2 years prior to Cycle 1 Day 1.
10. Prior radiotherapy ≤15 days prior to Cycle 1 Day 1, with the exception of a single
fraction of radiotherapy for the purposes of palliation, which is permitted.
11. Criterion modified per Amendment 2.
11.1. Corrected QT interval by the Fridericia correction formula (QTcF) on the
screening ECG >450 msec.
12. Receiving concomitant medications that prolong QTc and are unable to discontinue use
while receiving study drug (see Attachment 4).
13. History of clinically significant ventricular arrhythmias (eg, ventricular tachycardia,
ventricular fibrillation, torsades de pointes).
14. HIV positive subjects with 1 or more of the following:
a. Not receiving highly active antiretroviral therapy
b. A change in antiretroviral therapy within 6 months of the start of screening
(except if, after consultation with the sponsor on exclusion criterion 14.c, a change is made to avoid a potential drug-drug interaction with the study drug)
c. Receiving antiretroviral therapy that may interfere with the study drug (consult
the sponsor for review of medication prior to enrollment)
d. CD4 count <350 at screening
e. An acquired immunodeficiency syndrome-defining opportunistic infection
within 6 months of the start of screening
15. Criterion modified per Amendment 2.
15.1. ≤30 days prior to Cycle 1 Day 1 had:
a. a transfusion (platelets or red blood cells)
b. chemotherapy
c. hematopoietic growth factors
d. an investigational agent for prostate cancer
e. major surgery
1. Prior treatment with a PARP inhibitor.
2. Criterion modified per Amendment 2.
2.1. Prior platinum-based chemotherapy for the treatment of prostate cancer.
3. Known history or current diagnosis of myelodysplastic syndrome (MDS)/acute myeloid
leukemia (AML).
4. Known symptomatic or impending cord compression, except if subject has received
definitive treatment for this and demonstrates evidence of clinically stable disease.
5. Known symptomatic uncontrolled brain or leptomeningeal metastases (controlled is
defined as CNS disease which has undergone treatment [eg, radiation or surgery] at
least 15 days prior to Cycle 1 Day 1).
6. Known allergies, hypersensitivity, or intolerance to niraparib or its excipients (refer to
Investigator's Brochure).12
7. Any condition for which, in the opinion of the investigator, participation would not be
in the best interest of the subject (eg, compromise the well-being) or that could prevent,
limit, or confound the protocol-specified assessments.
8. Known disorder affecting gastrointestinal absorption.
9. Active cancer (other than prostate cancer; or basal cell or squamous cell skin cancer,
non-muscle invasive bladder cancer [stages pTaG1 and pTaG2], or any other cancer in
situ currently in complete remission) within 2 years prior to Cycle 1 Day 1.
10. Prior radiotherapy ≤15 days prior to Cycle 1 Day 1, with the exception of a single
fraction of radiotherapy for the purposes of palliation, which is permitted.
11. Criterion modified per Amendment 2.
11.1. Corrected QT interval by the Fridericia correction formula (QTcF) on the
screening ECG >450 msec.
12. Receiving concomitant medications that prolong QTc and are unable to discontinue use
while receiving study drug (see Attachment 4).
13. History of clinically significant ventricular arrhythmias (eg, ventricular tachycardia,
ventricular fibrillation, torsades de pointes).
14. HIV positive subjects with 1 or more of the following:
a. Not receiving highly active antiretroviral therapy
b. A change in antiretroviral therapy within 6 months of the start of screening
(except if, after consultation with the sponsor on exclusion criterion 14.c, a change is made to avoid a potential drug-drug interaction with the study drug)
c. Receiving antiretroviral therapy that may interfere with the study drug (consult
the sponsor for review of medication prior to enrollment)
d. CD4 count <350 at screening
e. An acquired immunodeficiency syndrome-defining opportunistic infection
within 6 months of the start of screening
15. Criterion modified per Amendment 2.
15.1. ≤30 days prior to Cycle 1 Day 1 had:
a. a transfusion (platelets or red blood cells)
b. chemotherapy
c. hematopoietic growth factors
d. an investigational agent for prostate cancer
e. major surgery
The Estimated Number of Participants
-
Taiwan
9 participants
-
Global
289 participants
