Ignite Creation Date:
2025-12-24 @ 7:45 PM
Ignite Modification Date:
2025-12-30 @ 7:29 PM
Study NCT ID:
NCT03076203
Status:
COMPLETED
Last Update Posted:
2025-04-29
First Post:
2017-02-21
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Phase IB Trial of Radium-223 and Niraparib in Patients With Castrate Resistant Prostate Cancer (NiraRad)
Sponsor:
Sidney Kimmel Cancer Center at Thomas Jefferson University
Organization:
Study Overview
Official Title:
Phase IB Trial of Radium-223 and Niraparib in Patients With Castrate Resistant Prostate Cancer (NiraRad)
Status:
COMPLETED
Status Verified Date:
2025-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase Ib trial studies the side effects and best dose of niraparib when given together with radium Ra223 dichloride in treating subjects with prostate cancer that keeps growing even when the amount of testosterone in the body is reduced to very low levels and has spread from the primary site to the bone. Radium Ra 223 dichloride, acts like calcium to target cancer in the bones and may deliver radiation directly to the bone tumors, limiting damage to the surrounding normal tissue. Niraparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving radium Ra 223 dichloride and niraparib may work better in treating subjects with hormone-resistant prostate cancer metastatic to the bone.
Detailed Description:
PRIMARY OBJECTIVES:
I. To determine a safe dose of niraparib when combined with radium Ra 223 dichloride (radium-223) in patients with metastatic castrate-resistant prostate cancer (mCRPC) that have and have not received prior chemotherapy.
SECONDARY OBJECTIVES:
I. To determine the proportion of subjects with 50% prostate-specific antigen (PSA) reduction from baseline in men treated with niraparib and radium 223.
II. To determine the radiographic PFS (rPFS) at 6 months in men treated with niraparib and radium 223.
III. To determine the proportion of subjects that have circulating tumor cell (CTC) conversion (\>= 5 to \< 5/7.5ml) confirmed in a second assessment \> 4 weeks later in men treated with niraparib and radium 223.
IV. To determine the overall progression-free survival in men treated with niraparib and radium 223.
V. To determine the time to total-ALP (alkaline phosphatase) progression defined in subjects with no total-ALP decline from baseline as \>= 25% increase from the baseline value, at least 12 weeks from baseline.
VI. To determine the time to total-ALP (alkaline phosphatase) progression defined in patient with an initial total-ALP decline from baselines as \>= 25% increase from the nadir value, which is confirmed by a second value obtained three or more weeks later.
VII. To determine the total-ALP normalization, defined as the return of total-ALP value to within normal range at 12 weeks in 2 consecutive measurements (at least 2 weeks apart) after that of treatment in subjects who have their ALP above upper limit of normal (ULN) at baseline.
VIII. To determine the long term safety-tolerability of the combination of niraparib and radium 223 in men treated with niraparib and radium 223.
TERTIARY OBJECTIVES:
I. Study of deoxyribonucleic acid (DNA) repair aberrations; whole exome and transcriptome in pre-therapy tumor biopsy samples.
II. Compare changes in bone marrow micro-environment (hematopoietic stem cell \[HSC\] niche\\ C-X-C motif chemokine ligand 12 \[CXCL12\]/C-X-C motif chemokine receptor 4 \[CXCR4\] axis) pre and post therapy in up to 10 men treated with niraparib and radium 223.
III. Evaluate the baseline plasma cell-free (cf)-DNA for aberrations in DNA repair genes such as breast cancer (BRCA)1, BRCA2, ataxia telangiectasia mutated (ATM), ataxia-telangiectasia and rad3-related (ATR), partner and localizer of brca2 gene (PALB2) as well as the androgen receptor (AR) gene via next generation sequencing.
IV. Compare gene expression changes in baseline and serial (at end of cycle 1 and 3) whole blood ribonucleic acid (RNA) (collect blood in edetic acid \[EDTA\] tubes and RNA-later) using Nanostring PanCancer and immunology panel.
V. Evaluate the baseline CTCs for nuclear androgen receptor (AR), phosphorylated (p) nuclear factor kappa-beta (NF-kB), and gamma-H2A histone family member X (H2AX) foci via immunostaining.
I. To determine a safe dose of niraparib when combined with radium Ra 223 dichloride (radium-223) in patients with metastatic castrate-resistant prostate cancer (mCRPC) that have and have not received prior chemotherapy.
SECONDARY OBJECTIVES:
I. To determine the proportion of subjects with 50% prostate-specific antigen (PSA) reduction from baseline in men treated with niraparib and radium 223.
II. To determine the radiographic PFS (rPFS) at 6 months in men treated with niraparib and radium 223.
III. To determine the proportion of subjects that have circulating tumor cell (CTC) conversion (\>= 5 to \< 5/7.5ml) confirmed in a second assessment \> 4 weeks later in men treated with niraparib and radium 223.
IV. To determine the overall progression-free survival in men treated with niraparib and radium 223.
V. To determine the time to total-ALP (alkaline phosphatase) progression defined in subjects with no total-ALP decline from baseline as \>= 25% increase from the baseline value, at least 12 weeks from baseline.
VI. To determine the time to total-ALP (alkaline phosphatase) progression defined in patient with an initial total-ALP decline from baselines as \>= 25% increase from the nadir value, which is confirmed by a second value obtained three or more weeks later.
VII. To determine the total-ALP normalization, defined as the return of total-ALP value to within normal range at 12 weeks in 2 consecutive measurements (at least 2 weeks apart) after that of treatment in subjects who have their ALP above upper limit of normal (ULN) at baseline.
VIII. To determine the long term safety-tolerability of the combination of niraparib and radium 223 in men treated with niraparib and radium 223.
TERTIARY OBJECTIVES:
I. Study of deoxyribonucleic acid (DNA) repair aberrations; whole exome and transcriptome in pre-therapy tumor biopsy samples.
II. Compare changes in bone marrow micro-environment (hematopoietic stem cell \[HSC\] niche\\ C-X-C motif chemokine ligand 12 \[CXCL12\]/C-X-C motif chemokine receptor 4 \[CXCR4\] axis) pre and post therapy in up to 10 men treated with niraparib and radium 223.
III. Evaluate the baseline plasma cell-free (cf)-DNA for aberrations in DNA repair genes such as breast cancer (BRCA)1, BRCA2, ataxia telangiectasia mutated (ATM), ataxia-telangiectasia and rad3-related (ATR), partner and localizer of brca2 gene (PALB2) as well as the androgen receptor (AR) gene via next generation sequencing.
IV. Compare gene expression changes in baseline and serial (at end of cycle 1 and 3) whole blood ribonucleic acid (RNA) (collect blood in edetic acid \[EDTA\] tubes and RNA-later) using Nanostring PanCancer and immunology panel.
V. Evaluate the baseline CTCs for nuclear androgen receptor (AR), phosphorylated (p) nuclear factor kappa-beta (NF-kB), and gamma-H2A histone family member X (H2AX) foci via immunostaining.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| JT 8649 | OTHER | JeffTrial Number | View |