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

• ClinicalTrials.gov Identifier: NCT02854436
• Recruitment Status: Completed
• First Posted: August 3, 2016
• Results First Posted: March 8, 2022
• Last Update Posted: November 13, 2023
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

Tracking Information

• First Submitted Date: August 1, 2016
• First Posted Date: August 3, 2016
• Results First Submitted Date: January 25, 2022
• Results First Posted Date: March 8, 2022
• Last Update Posted Date: November 13, 2023
• Actual Study Start Date: August 31, 2016
• Actual Primary Completion Date: January 26, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 7, 2022)

Objective Response Rate (ORR) for Participants With Measurable Metastatic Castration-resistant Prostate Cancer (mCRPC) and Breast Cancer Gene (BRCA) Mutation [ Time Frame: 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.

Original Primary Outcome Measures (submitted: August 1, 2016)

Response Rate (RR) [ Time Frame: From enrollment to completion of study (approximately 3 years and 2 months) ]

RR is defined as: objective response, or conversion of circulating tumor cells, or prostate specific antigen (PSA) decline of >=50 percent (%).

Current Secondary Outcome Measures (submitted: March 7, 2022)

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

Original Secondary Outcome Measures (submitted: August 1, 2016)

• Overall Survival (OS) [ Time Frame: From enrollment to completion of study (approximately up to 3 years and 2 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 (approximately up to 3 years and 2 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 (approximately up to 3 years and 2 months) ]
  Time to PSA progression is defined as the time to first PSA increase that is 25% 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 (approximately up to 3 years and 2 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 (approximately up to 3 years and 2 months) ]
• Duration of Objective Response [ Time Frame: From complete response (CR) or partial response (PR) to radiographic progression of disease (approximately up to 3 years and 2 months) ]
  Duration of objective response will be assessed in participants who achieved a CR or PR. The objective response rate (ORR) is defined as the percentage of participants who achieved a Complete response (CR) or partial response (PR) as best responses.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: An Efficacy and Safety Study of Niraparib in Men With Metastatic Castration-Resistant Prostate Cancer and DNA-Repair Anomalies
• Official Title: A Phase 2 Efficacy and Safety Study of Niraparib in Men With Metastatic Castration-Resistant Prostate Cancer and DNA-Repair Anomalies
• 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.
• 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 Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Prostatic Neoplasms

Intervention

Drug: Niraparib

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

Other Name: JNJ-64091742

Study Arms

Experimental: Niraparib

Participants will receive 300 milligram (mg) niraparib (3 capsules*100 mg) orally once daily.

Intervention: Drug: Niraparib

• Publications *: Smith MR, Scher HI, Sandhu S, Efstathiou E, Lara PN Jr, Yu EY, George DJ, Chi KN, Saad F, Stahl O, Olmos D, Danila DC, Mason GE, Espina BM, Zhao X, Urtishak KA, Francis P, Lopez-Gitlitz A, Fizazi K; GALAHAD investigators. Niraparib in patients with metastatic castration-resistant prostate cancer and DNA repair gene defects (GALAHAD): a multicentre, open-label, phase 2 trial. Lancet Oncol. 2022 Mar;23(3):362-373. doi: 10.1016/S1470-2045(21)00757-9. Epub 2022 Feb 4.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 25, 2021): 289
• Original Estimated Enrollment (submitted: August 1, 2016): 100
• Actual Study Completion Date: August 16, 2023
• Actual Primary Completion Date: January 26, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Belgium, Brazil, Canada, Denmark, France, Israel, Korea, Republic of, Netherlands, Russian Federation, Spain, Sweden, Taiwan, United Kingdom, United States
• Removed Location Countries: Germany

Administrative Information

• NCT Number: NCT02854436
• Other Study ID Numbers: CR108208; 64091742PCR2001 ( Other Identifier: Janssen Research & Development, LLC ); 2016-002057-38 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Janssen Research & Development, LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Janssen Research & Development, LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Janssen Research & Development, LLC
• Verification Date: November 2023