Clinical trial NCT02952534: A Study of Rucaparib in Patients With Metastatic Castration-resistant Prostate Cancer and Homologous Recombination Gene Deficiency
Official title: TRITON2: A Multicenter, Open-label Phase 2 Study of Rucaparib in Patients With Metastatic Castration-resistant Prostate Cancer Associated With Homologous Recombination Deficiency
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Castration Resistant Prostate Cancer
Keywords: CRPC
PARP inhibitor
PARPi
BRCA
ATM
HRD
TRITON
homologous recombination
DNA repair
DNA defect
DNA anomaly
BARD1
BRIP1
CDK12
CHEK2
FANCA
NBN
PALB2
RAD51
RAD51B
RAD51C
RAD51D
RAD54L
germline
somatic
mCRPC
Lead sponsor: pharmaand GmbH
Sponsor class: INDUSTRY
Collaborators: name: Foundation Medicine
First posted: 2016-11-02
Enrollment: 277
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 determine how patients with metastatic castration-resistant prostate cancer, and evidence of a homologous recombination gene deficiency, respond to treatment with rucaparib.


Eligibility criteria: Inclusion Criteria:

* Be 18 years old at the time the informed consent form is signed
* Have a histologically or cytologically confirmed adenocarcinoma or poorly differentiated carcinoma of the prostate
* Be surgically or medically castrated, with serum testosterone levels of ≤ 50 ng/dL (1.73 nM)
* Experienced disease progression after having received at least 1 but no more than 2 prior next-generation androgen receptor-targeted therapies, and 1 prior taxane-based chemotherapy, for castration-resistant disease
* Have a deleterious mutation in BRCA1/2 or ATM, or molecular evidence of other homologous recombination deficiency

Exclusion Criteria:

* Active second malignancy, with the exception of curatively treated non-melanoma skin cancer, carcinoma in situ, or superficial bladder cancer
* Prior treatment with any PARP inhibitor, mitoxantrone, cyclophosphamide or any platinum-based chemotherapy
* Symptomatic and/or untreated central nervous system metastases
* Pre-existing duodenal stent and/or any gastrointestinal disorder or defect that would, in the opinion of the investigator, interfere with absorption of rucaparib

Primary outcomes:
measure: Confirmed Objective Response Rate (ORR) by Gene in Patients With Measurable Disease at Baseline Per Central Independent Radiology Review (IRR)
timeFrame: Assessments every 8 weeks from study day 1 for the first 24 weeks, and then every 12 weeks until disease progression, death, or initiation of subsequent treatment. Total follow-up was up to approximately 3 years.
Secondary outcomes:
measure: Confirmed Objective Response Rate (ORR) by Gene in Patients With Measurable Disease at Baseline Per Investigator (INV)
timeFrame: Assessments every 8 weeks from study day 1 for the first 24 weeks, and then every 12 weeks until disease progression, death, or initiation of subsequent treatment. Total follow-up was up to approximately 3 years.
measure: Duration of Response (DOR) by Gene in Patients With Confirmed Response Per Central Independent Radiology Review (IRR)
timeFrame: Assessments every 8 weeks from study day 1 for the first 24 weeks, and then every 12 weeks until disease progression, death, or initiation of subsequent treatment. Total follow-up was up to approximately 3 years.
measure: Duration of Response (DOR) by Gene in Patients With Confirmed Response Per Investigator
timeFrame: Assessments every 8 weeks from study day 1 for the first 24 weeks, and then every 12 weeks until disease progression, death, or initiation of subsequent treatment. Total follow-up was up to approximately 3 years.
measure: Confirmed PSA Response (≥ 50% Decrease) by Gene as Assessed by Local Laboratory
timeFrame: PSA assessments were done at baseline, Week 5, Week 9, every 4 weeks thereafter, and at Treatment Discontinuation. Total follow-up was up to approximately 39 months.
measure: Confirmed PSA Response (≥ 90% Decrease) by Gene as Assessed by Local Laboratory
timeFrame: PSA assessments were done at baseline, Week 5, Week 9, every 4 weeks thereafter, and at Treatment Discontinuation. Total follow-up was up to approximately 39 months.
measure: Radiologic Progression-free Survival (rPFS) by Gene in All Patients Per Central Independent Radiology Review (IRR)
timeFrame: Assessments every 8 weeks from study day 1 for the first 24 weeks, and then every 12 weeks until disease progression, death, or initiation of subsequent treatment. Total follow-up was up to approximately 3 years.
measure: Radiologic Progression-free Survival (rPFS) by Gene in All Patients Per Investigator
timeFrame: Assessments every 8 weeks from study day 1 for the first 24 weeks, and then every 12 weeks until disease progression, death, or initiation of subsequent treatment. Total follow-up was up to approximately 3 years.
measure: Overall Survival (OS) by Gene
timeFrame: From date of first dose until event, loss to follow-up, withdrawal of consent, or study closure: an overall median of approximately 33.1 months
measure: Clinical Benefit Rate (CBR) by Gene Per Central Independent Radiology Review (IRR)
timeFrame: Assessments every 8 weeks from study day 1 for the first 24 weeks, and then every 12 weeks until disease progression, death, or initiation of subsequent treatment. Total follow-up was up to approximately 3 years.
measure: Clinical Benefit Rate (CBR) by Gene Per Investigator
timeFrame: Assessments every 8 weeks from study day 1 for the first 24 weeks, and then every 12 weeks until disease progression, death, or initiation of subsequent treatment. Total follow-up was up to approximately 3 years.
measure: Time to PSA Progression by Gene
timeFrame: PSA assessments were done at baseline, Week 5, Week 9, every 4 weeks thereafter, and at Treatment Discontinuation. Total follow-up was up to approximately 39 months.
measure: Steady State Trough (Cmin) Level Rucaparib Concentrations
timeFrame: Participants were assessed at Study Day 29, Day 57, Day 85 and Day 113
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Mayo Clinc
state: Arizona
city: Tucson
country: United States
facility: Arizona Oncology Associates
state: Arizona
city: Laguna Hills
country: United States
facility: Alliance Research Centers
state: California
city: Los Angeles
country: United States
facility: VA Greater Los Angeles Healthcare System
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: San Diego
country: United States
facility: Sharp Memorial Hospital
state: California
city: San Francisco
country: United States
facility: Pacific Hematology Oncology Associates
state: California
city: San Francisco
country: United States
facility: San Francisco VA Health Care System
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: Santa Rosa
country: United States
facility: Redwood Regional Medical Group
state: California
city: Vallejo
country: United States
facility: Kaiser Permanente Medical Center (Vallejo)
state: California
city: Aurora
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: New Haven
country: United States
facility: Yale School of Medicine
state: Connecticut
city: Newark
country: United States
facility: 4701 Ogletown Stanton Rd.
state: Delaware
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Boca Raton
country: United States
facility: Boca Raton Community Hospital, Inc.
state: Florida
city: Fort Myers
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Orlando
country: United States
facility: University of Florida Health Cancer Center
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Atlanta Urological Group
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Comprehensive Cancer Center
state: Illinois
city: New Orleans
country: United States
facility: Ochsner Medical Center
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland Greenebaum Cancer Center
state: Maryland
city: Bethesda
country: United States
facility: Walter Reed Hospital
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: VA Ann Arbor Healthcare System
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Edina
country: United States
facility: Fairview Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: Minnesota Oncology Hematology, P.A.
state: Minnesota
city: Minneapolis
country: United States
facility: Minnesota Veterans Research Institute
state: Minnesota
city: Kansas City
country: United States
facility: HCA Midwest Division - Kansas City
state: Missouri
city: Omaha
country: United States
facility: Alegent Health Bergan Mercy Hospital , GU Research Network
state: Nebraska
city: Omaha
country: United States
facility: Nebraska Cancer Specialists
state: Nebraska
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Lawrenceville
country: United States
facility: Premier Urology Associates dba/AdvanceMed Research
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park
state: New York
city: New York
country: United States
facility: NYU Perlmutter Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering CC
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College/NewYork-Presbyterian Hospital
state: New York
city: Poughkeepsie
country: United States
facility: Premier Medical Group of the Hudson Valley PC
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Concord
country: United States
facility: Carolina Urology Partners
state: North Carolina
city: Cincinnati
country: United States
facility: The Urology Group
state: Ohio
city: Kettering
country: United States
facility: Kettering Cancer Center
state: Ohio
city: Middleburg Heights
country: United States
facility: Clinical Research Solutions
state: Ohio
city: Portland
country: United States
facility: VA Portland Health Care System
state: Oregon
city: Horsham
country: United States
facility: Consultants in Medical Oncology Hematology
state: Pennsylvania
city: Nashville
country: United States
facility: SCRI - Tennessee Oncology
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology Medical City Dallas
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: UT Health Science Center
state: Texas
city: Tyler
country: United States
facility: Texas Oncology - Tyler
state: Texas
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Seattle
country: United States
facility: VA Puget Sound
state: Washington
city: Saint Leonards
country: Australia
facility: Northern Cancer Insitute, St. Leonards
state: New South Wales
city: Hobart
country: Australia
facility: Royal Hobart Hospital
state: Tasmania
city: Frankston
country: Australia
facility: Peninsula & Southeast Oncology
state: Victoria
city: Geelong
country: Australia
facility: Barwon Health, University Hospital Geelong
state: Victoria
city: Malvern
country: Australia
facility: Cabrini Hospital
state: Victoria
city: Miranda
country: Australia
facility: Southside Cancer Care Centre
city: Orange
country: Australia
facility: Orange Health Services
city: Subiaco
country: Australia
facility: St John of God Hospital, Subiaco
city: Wagga Wagga
country: Australia
facility: Riverina Cancer Care Centre
city: Antwerp
country: Belgium
facility: ZNA Middelheim
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Kortrijk
country: Belgium
facility: AZ Groeninge
city: Liège
country: Belgium
facility: CHU Sart-Tilman
city: Liège
country: Belgium
facility: Equipe de Recherche Clinique, Département d'Oncologie/Hématologie
city: Roeselare
country: Belgium
facility: AZ DELTA
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre Hamilton Health Services
state: Ontario
city: London
country: Canada
facility: London Health Science Center - Victoria Hospital
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
city: Copenhagen
country: Denmark
facility: Copenhagen University Hospital
city: Herlev
country: Denmark
facility: Herlev Hospital
city: Vejle
country: Denmark
facility: Vejle Sygehus
city: Caen
country: France
facility: Centre François Baclesse
city: Dijon
country: France
facility: Centre Georges François Leclerc
city: Le Mans
country: France
facility: Clinique Victor Hugo Centre Jean Bernard
city: Lille
country: France
facility: Hôpital Privé La Louvière
city: Nancy
country: France
facility: Polyclinique de Gentilly (Centre D'Oncologie De Gentilly)
city: Paris
country: France
facility: Institut Curie
city: Plérin
country: France
facility: Hôpital Privé des Côtes d'Armor
city: Rennes
country: France
facility: CRLCC Eugene Marquis
city: Augsburg
country: Germany
facility: Gemeinschaftspraxis fur Hamatologie & Onkologie
city: Berlin
country: Germany
facility: Charite Universitatsmedizin Berlin
city: Dresden
country: Germany
facility: Universitatsklinikum Carl Gustav Carus
city: Dusseldorf
country: Germany
facility: Universitatsklinikum Dusseldorf
city: Emmendingen
country: Germany
facility: Urologische Gemeinschaftspraxis
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg-Eppendorf (UKE)
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg
city: Jena
country: Germany
facility: Universitatsklinikum Jena
city: Köln
country: Germany
facility: Universitätsklinik Köln
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein
city: Mannheim
country: Germany
facility: Medizinischen Fakultät Mannheim der Universität Heidelberg
city: Nürtingen
country: Germany
facility: Studienpraxis Urologie
city: Tuebingen
country: Germany
facility: University of Tuebingen
city: Wuppertal
country: Germany
facility: Die Gesundhehitsunion DGU
city: Cork
country: Ireland
facility: Cork University Hospital
city: Dublin
country: Ireland
facility: St. Vincent's University Hospital
city: Dublin
country: Ireland
facility: St James's Hospital
city: Dublin
country: Ireland
facility: Adelaide & Meath Hospital, Incorporating the National Children's Hospital
city: Dublin
country: Ireland
facility: Mater Misericordiae University Hospital
city: Haifa
country: Israel
facility: Rambam Health Care Campus (RHCC), Rambam Medical Center
city: Jerusalem
country: Israel
facility: Hadassah University Hospital
city: Kfar Saba
country: Israel
facility: Meir Medical Center
city: Petach Tikva
country: Israel
facility: Rabin Medical Center-Beilinson Campus
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Tel Aviv
country: Israel
facility: The Tel Aviv Sourasky Medical Center (Ichilov Hospital)
city: Arezzo
country: Italy
facility: Ospedale San Donato, Azienda USLSUDEST
city: Faenza
country: Italy
facility: Ospedale Santa Maria delle Croci
city: Milano
country: Italy
facility: IRCCS Istituto Nazionale dei Tumori (INT)
city: Milano
country: Italy
facility: IEO Instituto Europeo di Oncologia
city: Modena
country: Italy
facility: University of Modena and Reggio Emilia Medical Oncology
city: Rome
country: Italy
facility: Azienda Ospedaliera San Camillo-Forlanini
city: Terni
country: Italy
facility: Azienda Opsedaliera S. Maria di Terni
city: Trento
country: Italy
facility: Santa Chiara Hospital, Dept Medical Oncology
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital del Mar, Servicio de Oncología
city: Barcelona
country: Spain
facility: Hospital Clínic i Provincial de Barcelona-Oncology
city: Barcelona
country: Spain
facility: Instituto Catalan de Oncologia
city: Barcelona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
city: Guadalajara
country: Spain
facility: Hospital General Universitario de Guadalajara
city: Lugo
country: Spain
facility: Hospital Universitario Lucus Augusti.
city: Madrid
country: Spain
facility: MD Anderson Cancer Center - Madrid
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Hospital Puerta de Hierro-Majadahonda
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
city: Sabadell
country: Spain
facility: Corporacio Sanitaria Parc Tauli
city: Santander
country: Spain
facility: Marques de Valdecilla University Hospital (HUMV)
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncologia IVO
city: Slough
country: United Kingdom
facility: Wexham Park Hospital
state: Berkshire
city: Northwood
country: United Kingdom
facility: Mount Vernon Cancer Centre
state: England
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital
state: Surrey
city: Headington
country: United Kingdom
facility: Oxford University Hospitals
city: Liverpool
country: United Kingdom
facility: Royal Liverpool Hospital
city: London
country: United Kingdom
facility: London Health Science Center - Victoria Hospital
city: London
country: United Kingdom
facility: Guy's Hospital
city: London
country: United Kingdom
facility: Sarah Cannon Research Institutute - UK
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
city: Taunton
country: United Kingdom
facility: Musgrove Park Hospital
city: Wirral
country: United Kingdom
facility: The Clatterbridge Cancer Centre NHS Foundation Trust
Study officials:
References:
citation: Green ML, Ma SC, Goble S, Giordano H, Maloney L, Simmons AD, Beltman J, Harding TC, Xiao JJ. Population pharmacokinetics of rucaparib in patients with advanced ovarian cancer or other solid tumors. Cancer Chemother Pharmacol. 2022 May;89(5):671-682. doi: 10.1007/s00280-022-04413-7. Epub 2022 Apr 10.
citation: Maia MC, Salgia M, Pal SK. Harnessing cell-free DNA: plasma circulating tumour DNA for liquid biopsy in genitourinary cancers. Nat Rev Urol. 2020 May;17(5):271-291. doi: 10.1038/s41585-020-0297-9. Epub 2020 Mar 17.