Clinical trial NCT02975934: A Study of Rucaparib Versus Physician's Choice of Therapy in Participants With Metastatic Castration-resistant Prostate Cancer and Homologous Recombination Gene Deficiency
Official title: TRITON3: A Multicenter, Randomized, Open Label Phase 3 Study of Rucaparib Versus Physician's Choice of Therapy for Patients With Metastatic Castration Resistant Prostate Cancer Associated With Homologous Recombination Deficiency
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Metastatic Castration Resistant Prostate Cancer
Keywords: CRPC
PARP inhibitor
PARPi
BRCA
ATM
HRD
TRITON
homologous recombination
DNA repair
DNA defect
DNA anomaly
germline
somatic
mCRPC
Lead sponsor: pharmaand GmbH
Sponsor class: INDUSTRY
Collaborators: name: Foundation Medicine
First posted: 2016-11-29
Enrollment: 405
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine how participants with metastatic castration-resistant prostate cancer, and evidence of a homologous recombination gene deficiency, respond to treatment with rucaparib versus treatment with physician's choice of abiraterone acetate, enzalutamide, or docetaxel.


Eligibility criteria: Inclusion Criteria:

* Be 18 years old at the time the informed consent is signed
* Have a histologically or cytologically confirmed adenocarcinoma or poorly differentiated carcinoma of the prostate that is metastatic
* Be surgically or medically castrated, with serum testosterone levels of ≤ 50 ng/dL (1.73 nM)
* Be eligible for treatment with physician's choice of comparator treatment (abiraterone acetate, enzalutamide or docetaxel)
* Experienced disease progression after having received 1 prior next generation androgen receptor-targeted therapy
* Have a deleterious mutation in a BRCA1/2 or ATM gene

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
* Prior treatment with chemotherapy for metastatic castration-resistant prostate cancer
* 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 study drug

Primary outcomes:
measure: Radiographic Progression-free Survival (rPFS) by IRR in Participants With a BRCA Alteration
timeFrame: From enrollment to primary completion of study (Total follow-up was up to approximately 4 years)
measure: Radiographic Progression-free Survival (rPFS) by IRR in Participants With a BRCA or ATM Alteration Combined
timeFrame: From enrollment to primary completion of study (Total follow-up was up to approximately 4 years)
Secondary outcomes:
measure: Interim Overall Survival in Participants With a BRCA Alteration
timeFrame: From enrollment to primary completion of study (up to approximately 5 years)
measure: Interim Overall Survival in Participants With a BRCA or ATM Alteration Combined
timeFrame: From enrollment to primary completion of study (up to approximately 5 years)
measure: Objective Response Rate (ORR) by IRR in Participants With a BRCA Alteration
timeFrame: From enrollment to primary completion of study (Total follow-up was up to approximately 4 years)
measure: Objective Response Rate (ORR) by IRR in Participants With a BRCA or ATM Alteration Combined
timeFrame: From enrollment to primary completion of study (Total follow-up was up to approximately 4 years)
measure: Duration of Response (DOR) by IRR in Participants With a BRCA Alteration
timeFrame: From enrollment to primary completion of study (Total follow-up was up to approximately 4 years)
measure: Duration of Response (DOR) by IRR in Participants With a BRCA or ATM Alteration Combined
timeFrame: From enrollment to primary completion of study (Total follow-up was up to approximately 4 years)
measure: PSA Response in Participants With a BRCA Alteration
timeFrame: From enrollment to primary completion of study (up to approximately 5 years)
measure: PSA Response in Participants With a BRCA or ATM Alteration Combined
timeFrame: From enrollment to primary completion of study (up to approximately 5 years)
measure: Clinical Benefit Rate (CBR) by IRR at 6 Months in Participants With a BRCA Alteration
timeFrame: From enrollment to 6 months
measure: Clinical Benefit Rate (CBR) by IRR at 6 Months in Participants With a BRCA or ATM Alteration Combined
timeFrame: From enrollment to 6 months
measure: Time to Prostate Specific Antigen (PSA) Progression in Participants With a BRCA Alteration
timeFrame: From enrollment to primary completion of study (up to approximately 5 years)
measure: Time to Prostate Specific Antigen (PSA) Progression in Participants With a BRCA or ATM Alteration Combined
timeFrame: From enrollment to primary completion of study (up to approximately 5 years)
measure: Change in Patient-reported Outcome (PRO) in Participants With a BRCA Alteration: FACT-P
timeFrame: From enrollment to up to approximately 25 weeks
measure: Change in Patient-reported Outcome (PRO) in Participants With a BRCA Alteration: BPI-SF
timeFrame: From enrollment to up to approximately 25 weeks
measure: Change in Patient-reported Outcome (PRO) in Participants With a BRCA Alteration: EQ-5D-5L
timeFrame: From enrollment to up to approximately 25 weeks
measure: Trough Plasma PK (Cmin) of Rucaparib Based on Sparse Sampling
timeFrame: From enrollment to week 5 of dosing
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Mayo Clinic - Arizona
state: Arizona
city: Tucson
country: United States
facility: Arizona Oncology Associates - USOR
state: Arizona
city: Beverly Hills
country: United States
facility: University of Southern California
state: California
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: San Bernardino
country: United States
facility: San Bernardino Urological Associates
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: St. Joseph Heritage Healthcare
state: California
city: Vallejo
country: United States
facility: Kaiser Permanente, Northern CA
state: California
city: Aurora
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Newark
country: United States
facility: Medical Oncology Hematology Consultants - USOR
state: Delaware
city: Boca Raton
country: United States
facility: Boca Raton Community Hospital, Inc.
state: Florida
city: Orlando
country: United States
facility: University of Florida Health Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Atlanta Urological Group
state: Georgia
city: Honolulu
country: United States
facility: Kaiser Permanente Medical Group
state: Hawaii
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 National Military Medical Center
state: Maryland
city: Columbia
country: United States
facility: Maryland Oncology Hematology P.A.
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: 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: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic - Rochester, MN
state: Minnesota
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
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
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: Chapel Hill
country: United States
facility: University of North Carolina Lineberger Cancer Center
state: North Carolina
city: Concord
country: United States
facility: Carolina Urology Partners
state: North Carolina
city: Durham
country: United States
facility: Durham VA Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: Oncology Hematology Care
state: Ohio
city: Cincinnati
country: United States
facility: The Urology Group
state: Ohio
city: Kettering
country: United States
facility: Kettering Medical 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: Portland
country: United States
facility: Northwest Cancer Specialist DBA Compass Oncology
state: Oregon
city: Portland
country: United States
facility: Knight Cancer Institute
state: Oregon
city: Nashville
country: United States
facility: Urology Associates Clinical Research
state: Tennessee
city: Dallas
country: United States
facility: Urology Clinics of North Texas
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: Round Rock
country: United States
facility: Texas Oncology Cancer Center-Round Rock
state: Texas
city: Virginia Beach
country: United States
facility: Urology of Virginia
state: Virginia
city: Gig Harbor
country: United States
facility: MultiCare Regional Cancer Center - Gig Harbor
state: Washington
city: Seattle
country: United States
facility: VA Puget Sound HCS
state: Washington
city: Seattle
country: United States
facility: University of Washington Fred Hutchinson Cancer Research Center
state: Washington
city: Miranda
country: Australia
facility: Southside Cancer Care Centre
state: New South Wales
city: Orange
country: Australia
facility: Orange Health Service
state: New South Wales
city: Saint Leonards
country: Australia
facility: Northern Cancer Insitute, St. Leonards
state: New South Wales
city: Subiaco
country: Australia
facility: St John of God Hospital, Subiaco
state: Western Australia
city: Frankston
country: Australia
facility: Peninsula & Southeast Oncology
city: Geelong
country: Australia
facility: Barwon Health, University Hospital Geelong
city: Hobart
country: Australia
facility: Royal Hobart Hospital
city: Wagga Wagga
country: Australia
facility: Riverina Cancer Care Centre
city: Antwerp
country: Belgium
facility: ZNA Middelheim
city: Kortrijk
country: Belgium
facility: AZ Groeninge
city: Liège
country: Belgium
facility: CHU Sart-Tilman
city: Namur
country: Belgium
facility: Clinique et Maternité Sainte-Elisabeth
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Winnipeg
country: Canada
facility: Cancer Care Manitoba
state: Manitoba
city: Moncton
country: Canada
facility: Centre Hospitalier Universitaire Dr-Georges-L.-Dumont
state: New Brunswick
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Oshawa
country: Canada
facility: Lakeridge Health Medical Specialty Medical Oncology
city: Toronto
country: Canada
facility: Sunnybrook Odette Cancer Centre
city: Copenhagen
country: Denmark
facility: Copenhagen University Hospital
city: Herlev
country: Denmark
facility: Herlev Hospital
city: Vejle
country: Denmark
facility: Vejle Sygehus
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: Lyon
country: France
facility: Centre Léon Bérard
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: Centre Armoricain de Radiotherapie, Imagerie medicale et Oncologie, CARIO
city: Rennes
country: France
facility: CRLCC Eugene Marquis
city: Villejuif
country: France
facility: Institut Gustave-Roussy
city: Augsburg
country: Germany
facility: Gemeinschaftspraxis für Hämatologie&Onkologie
city: Berlin
country: Germany
facility: Charite - Universitaetsmedizin Berlin
city: Braunschweig
country: Germany
facility: Apotheke des Städtischen Klinikums Braunschweig
city: Dresden
country: Germany
facility: University Hospital 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: Jena
country: Germany
facility: Universitatsklinikum Jena
city: Köln
country: Germany
facility: Universitätsklinikum Köln
city: Lubeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein
city: Mannheim
country: Germany
facility: Medizinischen Fakultät Mannheim der Universität Heidelberg
city: Nurtingen
country: Germany
facility: Studienpraxis Urologie
city: Tuebingen
country: Germany
facility: University of Tuebingen
city: Wuppertal
country: Germany
facility: Die GesundheitsUnion (DGU)
city: Cork
country: Ireland
facility: Cork University 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: Dublin
country: Ireland
facility: Mater Private Hospital (MPH)
city: Dublin
country: Ireland
facility: St James's Hospital
city: Dublin
country: Ireland
facility: St. Vincent's 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: Tel Aviv
country: Israel
facility: The Tel Aviv Sourasky Medical Center (Ichilov Hospital)
city: Tel Hashomer
country: Israel
facility: Chaim Sheba Medical Center
city: Arezzo
country: Italy
facility: Ospedale San Donato, Azienda USLSUDEST
city: Faenza
country: Italy
facility: Ospedale Santa Maria delle Croci
city: Meldola
country: Italy
facility: Romagnolo per lo Studio e la Cura dei Tumori IRST-IRCCS - Oncologia medica
city: Milano
country: Italy
facility: IEO Instituto Europeo di Oncologia
city: Modena
country: Italy
facility: University of Modena and Reggio Emilia
city: Roma
country: Italy
facility: Azienda Ospedaliera San Camillo-Forlanini
city: Terni
country: Italy
facility: Azienda Opsedaliera S. Maria di Terni
city: Trento
country: Italy
facility: Presidio Ospedaliero Santa Chiara di Trento
city: Barcelona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofia
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: Málaga
country: Spain
facility: Hospital Clinico Universitario Virgen de la Victoria
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 Oncología
city: London
country: United Kingdom
facility: Guy's and St Thomas' NHS Foundation Trust
state: England
city: London
country: United Kingdom
facility: Royal Marsden Hospital
state: England
city: Oxford
country: United Kingdom
facility: Oxford Cancer Centre, Medical Oncology Unit
state: England
city: Preston
country: United Kingdom
facility: Royal Preston Hospital
state: England
city: Slough
country: United Kingdom
facility: Wexham Park Hospital
state: England
city: Cardiff
country: United Kingdom
facility: Velindre Hospital
city: London
country: United Kingdom
facility: Royal Marsden 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: Fizazi K, Piulats JM, Reaume MN, Ostler P, McDermott R, Gingerich JR, Pintus E, Sridhar SS, Bambury RM, Emmenegger U, Lindberg H, Morris D, Nole F, Staffurth J, Redfern C, Saez MI, Abida W, Daugaard G, Heidenreich A, Krieger L, Sautois B, Loehr A, Despain D, Heyes CA, Watkins SP, Chowdhury S, Ryan CJ, Bryce AH; TRITON3 Investigators. Rucaparib or Physician's Choice in Metastatic Prostate Cancer. N Engl J Med. 2023 Feb 23;388(8):719-732. doi: 10.1056/NEJMoa2214676. Epub 2023 Feb 16.
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.