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

Prostatic Neoplasms Clinical Trial

— Galahad  

Official title:

A Phase 2 Efficacy and Safety Study of Niraparib in Men With Metastatic Castration-Resistant Prostate Cancer and DNA-Repair Anomalies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02854436
• Other study ID #: CR108208
• Secondary ID: 64091742PCR20012
• Status: Completed
• Phase: Phase 2
• Start date: August 31, 2016
• Est. completion date: August 16, 2023

Study information

• Verified date: November 2023
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 289
• Est. completion date: August 16, 2023
• Est. primary completion date: January 26, 2021
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Prostatic Neoplasms

Intervention

Drug:
• Niraparib
Participants will receive 300 mg niraparib (3 capsules*100 mg) orally once daily.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Brazil,  Canada,  Denmark,  France,  Israel,  Korea, Republic of,  Netherlands,  Russian Federation,  Spain,  Sweden,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR) for Participants With Measurable Metastatic Castration-resistant Prostate Cancer (mCRPC) and Breast Cancer Gene (BRCA) Mutation	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.	Up to 52 months
Secondary	Objective Response Rate for Participants With Measurable Metastatic Castration-resistant Prostate Cancer (mCRPC) and Non-Breast Cancer Gene (BRCA) Mutation	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.	Up to 52 months
Secondary	Circulating Tumor Cells (CTC) Response Rate	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.	At 8 weeks post-baseline
Secondary	Overall Survival (OS)	OS is defined as time from enrollment to death from any cause.	Up to 52 months
Secondary	Radiographic Progression-Free Survival (rPFS)	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.	Up to 52 months
Secondary	Time to Radiographic Progression	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.	Up to 52 months
Secondary	Time to Prostate-Specific Antigen (PSA) Progression	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.	Up to 52 months
Secondary	Time to Symptomatic Skeletal Event (SSE)	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.	Up to 52 months
Secondary	Duration of Objective Response	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.	Up to 52 months
Secondary	Number of Participants With Adverse Events (AEs)	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.	Up to 52 months
Secondary	Number of Participants With Worst Toxicity Grades for Clinical Laboratory Tests Based on National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE)	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).	Up to 52 months