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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Prostatic Neoplasms
• Intervention / Treatment: Drug: Niraparib

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
• Enrollment (Actual): 289
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Camperdown, Australia
  • Darlinghurst, Australia
  • East Albury, Australia
  • Kurralta Park, Australia
  • Macquarie University, Australia
  • Melbourne, Australia
  • Murdoch, Australia
  • Port Macquarie, Australia
  • Randwick, Australia
  • Wahroonga, Australia
• Belgium
  • Aalst, Belgium
  • Brussel, Belgium
  • Charleroi, Belgium
  • Gent, Belgium
  • Haine-Saint-Paul, La Louviere, Belgium
  • Hasselt, Belgium
  • Kortrijk, Belgium
  • Liège, Belgium
  • Namur, Belgium
  • Ottignies, Belgium
  • Wilrijk, Belgium
• Brazil
  • Barretos, Brazil
  • Belo Horizonte, Brazil
  • Curitiba, Brazil
  • Fortaleza, Brazil
  • Ijui, Brazil
  • Itajai, Brazil
  • Joinville, Brazil
  • Natal, Brazil
  • Salvador, Brazil
  • Sao Paulo, Brazil
• Canada
  • Quebec, Canada
  • British Columbia
    • Vancouver, British Columbia, Canada
  • Ontario
    • Oshawa, Ontario, Canada
    • Toronto, Ontario, Canada
  • Quebec
    • Montreal, Quebec, Canada
• Denmark
  • Aarhus N., Denmark
  • Copenhagen N, Denmark
  • Herlev, Denmark
  • Odense C, Denmark
• France
  • Avignon Cedex 9, France
  • Besancon, France
  • Caen, France
  • Lyon, France
  • Nice Cedex 2, France
  • Paris, France
  • Reims, France
  • Strasbourg, France
  • Villejuif Cedex, France
• Israel
  • Beer-Sheva, Israel
  • Haifa, Israel
  • Kfar Saba, Israel
  • Ramat Gan, Israel
  • Zrifin, Israel
• Korea, Republic of
  • Seoul, Korea, Republic of
• Netherlands
  • Alkmaar, Netherlands
  • Amsterdam, Netherlands
  • Groningen, Netherlands
  • Maastricht, Netherlands
  • Rotterdam, Netherlands
• Russian Federation
  • Moscow, Russian Federation
  • Omsk, Russian Federation
  • Tomsk, Russian Federation
• Spain
  • Barcelona, Spain
  • Córdoba, Spain
  • Madrid, Spain
  • Málaga, Spain
  • Pozuelo de Alarcon, Spain
  • Santander, Spain
  • Santiago de Compostela, Spain
  • Sevilla, Spain
  • Valencia, Spain
• Sweden
  • Göteborg, Sweden
  • Lund, Sweden
  • Stockholm, Sweden
  • Umeå, Sweden
• Taiwan
  • Kaohsiung, Taiwan
  • Taichung, Taiwan
  • Tainan, Taiwan
  • Taipei, Taiwan
  • Taoyuan County, Taiwan
• United Kingdom
  • Blackburn, United Kingdom
  • Bristol, United Kingdom
  • Cardiff, United Kingdom
  • Exeter, United Kingdom
  • London, United Kingdom
  • Preston, United Kingdom
• United States
  • Arizona
    • Tucson, Arizona, United States
  • California
    • Los Angeles, California, United States
    • Riverside, California, United States
    • Sacramento, California, United States
  • Colorado
    • Aurora, Colorado, United States
    • Denver, Colorado, United States
  • Illinois
    • Evanston, Illinois, United States
  • Kentucky
    • Danville, Kentucky, United States
    • Louisville, Kentucky, United States
  • Louisiana
    • New Orleans, Louisiana, United States
  • Massachusetts
    • Boston, Massachusetts, United States
  • Michigan
    • Detroit, Michigan, United States
  • Nebraska
    • Omaha, Nebraska, United States
  • New York
    • New York, New York, United States
  • North Carolina
    • Durham, North Carolina, United States
  • Pennsylvania
    • Lancaster, Pennsylvania, United States
    • Philadelphia, Pennsylvania, United States
  • South Carolina
    • Myrtle Beach, South Carolina, United States
  • Texas
    • Houston, Texas, United States
  • Virginia
    • Charlottesville, Virginia, United States
    • Fairfax, Virginia, United States
  • Washington
    • Seattle, Washington, United States
  • Wisconsin
    • Madison, Wisconsin, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

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

Collaborators and Investigators

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

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2016
• Primary Completion (Actual): January 26, 2021
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: August 1, 2016
• First Submitted That Met QC Criteria: August 1, 2016
• First Posted (Estimated): August 3, 2016

Study Record Updates

• Last Update Posted (Actual): September 14, 2023
• Last Update Submitted That Met QC Criteria: September 12, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: PARP inhibitor; Prostate cancer; Niraparib; CRPC; PARPi; Prostate neoplasm; Metastatic castrate-resistant prostate cancer; Galahad; DNA anomalies; DNA defect
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Congenital Abnormalities; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Poly(ADP-ribose) Polymerase Inhibitors; Niraparib
• Other Study ID Numbers: CR108208; 64091742PCR2001 (Other Identifier: Janssen Research & Development, LLC); 2016-002057-38 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No