Clinical trial NCT02854436: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostatic Neoplasms
Keywords: Prostate cancer
CRPC
Metastatic castrate-resistant prostate cancer
Prostate neoplasm
Galahad
Niraparib
DNA anomalies
DNA defect
PARP inhibitor
PARPi
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2016-08-03
Enrollment: 289
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Objective Response Rate (ORR) for Participants With Measurable Metastatic Castration-resistant Prostate Cancer (mCRPC) and Breast Cancer Gene (BRCA) Mutation
timeFrame: Up to 52 months
Secondary outcomes:
measure: Objective Response Rate for Participants With Measurable Metastatic Castration-resistant Prostate Cancer (mCRPC) and Non-Breast Cancer Gene (BRCA) Mutation
timeFrame: Up to 52 months
measure: Circulating Tumor Cells (CTC) Response Rate
timeFrame: At 8 weeks post-baseline
measure: Overall Survival (OS)
timeFrame: Up to 52 months
measure: Radiographic Progression-Free Survival (rPFS)
timeFrame: Up to 52 months
measure: Time to Radiographic Progression
timeFrame: Up to 52 months
measure: Time to Prostate-Specific Antigen (PSA) Progression
timeFrame: Up to 52 months
measure: Time to Symptomatic Skeletal Event (SSE)
timeFrame: Up to 52 months
measure: Duration of Objective Response
timeFrame: Up to 52 months
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Up to 52 months
measure: Number of Participants With Worst Toxicity Grades for Clinical Laboratory Tests Based on National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE)
timeFrame: Up to 52 months
Other outcomes:
Locations:
city: Tucson
country: United States
state: Arizona
city: Los Angeles
country: United States
state: California
city: Riverside
country: United States
state: California
city: Sacramento
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Denver
country: United States
state: Colorado
city: Evanston
country: United States
state: Illinois
city: Danville
country: United States
state: Kentucky
city: Louisville
country: United States
state: Kentucky
city: New Orleans
country: United States
state: Louisiana
city: Boston
country: United States
state: Massachusetts
city: Detroit
country: United States
state: Michigan
city: Omaha
country: United States
state: Nebraska
city: New York
country: United States
state: New York
city: Durham
country: United States
state: North Carolina
city: Lancaster
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Myrtle Beach
country: United States
state: South Carolina
city: Houston
country: United States
state: Texas
city: Charlottesville
country: United States
state: Virginia
city: Fairfax
country: United States
state: Virginia
city: Seattle
country: United States
state: Washington
city: Madison
country: United States
state: Wisconsin
city: Camperdown
country: Australia
city: Darlinghurst
country: Australia
city: East Albury
country: Australia
city: Kurralta Park
country: Australia
city: Macquarie University
country: Australia
city: Melbourne
country: Australia
city: Murdoch
country: Australia
city: Port Macquarie
country: Australia
city: Randwick
country: Australia
city: Wahroonga
country: Australia
city: Aalst
country: Belgium
city: Brussel
country: Belgium
city: Charleroi
country: Belgium
city: Gent
country: Belgium
city: Haine-Saint-Paul
country: Belgium
city: Hasselt
country: Belgium
city: Kortrijk
country: Belgium
city: Liège
country: Belgium
city: Namur
country: Belgium
city: Ottignies
country: Belgium
city: Wilrijk
country: Belgium
city: Barretos
country: Brazil
city: Belo Horizonte
country: Brazil
city: Curitiba
country: Brazil
city: Fortaleza
country: Brazil
city: Ijui
country: Brazil
city: Itajai
country: Brazil
city: Joinville
country: Brazil
city: Natal
country: Brazil
city: Salvador
country: Brazil
city: Sao Paulo
country: Brazil
city: Vancouver
country: Canada
state: British Columbia
city: Oshawa
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Quebec
country: Canada
city: Aarhus N.
country: Denmark
city: Copenhagen N
country: Denmark
city: Herlev
country: Denmark
city: Odense C
country: Denmark
city: Avignon Cedex 9
country: France
city: Besancon
country: France
city: Caen
country: France
city: Lyon
country: France
city: Nice Cedex 2
country: France
city: Paris
country: France
city: Reims
country: France
city: Strasbourg
country: France
city: Villejuif Cedex
country: France
city: Beer-Sheva
country: Israel
city: Haifa
country: Israel
city: Kfar Saba
country: Israel
city: Ramat Gan
country: Israel
city: Zrifin
country: Israel
city: Seoul
country: Korea, Republic of
city: Alkmaar
country: Netherlands
city: Amsterdam
country: Netherlands
city: Groningen
country: Netherlands
city: Maastricht
country: Netherlands
city: Rotterdam
country: Netherlands
city: Moscow
country: Russian Federation
city: Omsk
country: Russian Federation
city: Tomsk
country: Russian Federation
city: Barcelona
country: Spain
city: Córdoba
country: Spain
city: Madrid
country: Spain
city: Málaga
country: Spain
city: Pozuelo de Alarcon
country: Spain
city: Santander
country: Spain
city: Santiago de Compostela
country: Spain
city: Sevilla
country: Spain
city: Valencia
country: Spain
city: Göteborg
country: Sweden
city: Lund
country: Sweden
city: Stockholm
country: Sweden
city: Umeå
country: Sweden
city: Kaohsiung
country: Taiwan
city: Taichung
country: Taiwan
city: Tainan
country: Taiwan
city: Taipei
country: Taiwan
city: Taoyuan County
country: Taiwan
city: Blackburn
country: United Kingdom
city: Bristol
country: United Kingdom
city: Cardiff
country: United Kingdom
city: Exeter
country: United Kingdom
city: London
country: United Kingdom
city: Preston
country: United Kingdom
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.