A Study of Rucaparib in Patients With Metastatic Castration-resistant Prostate Cancer and Homologous Recombination Gene Deficiency

Metastatic Castration Resistant Prostate Cancer Clinical Trial

— TRITON2  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02952534
• Other study ID #: CO-338-052
• Secondary ID: 2016-003162-13
• Status: Completed
• Phase: Phase 2
• Start date: February 15, 2017
• Est. completion date: July 27, 2021

Study information

• Verified date: June 2023
• Source: zr Pharma & GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 277
• Est. completion date: July 27, 2021
• Est. primary completion date: July 18, 2021
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Metastatic Castration Resistant Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Rucaparib
Rucaparib will be administered daily

Locations

Country	Name	City	State
Australia	Peninsula & Southeast Oncology	Frankston	Victoria
Australia	Barwon Health, University Hospital Geelong	Geelong	Victoria
Australia	Royal Hobart Hospital	Hobart	Tasmania
Australia	Cabrini Hospital	Malvern	Victoria
Australia	Southside Cancer Care Centre	Miranda
Australia	Orange Health Services	Orange
Australia	Northern Cancer Insitute, St. Leonards	Saint Leonards	New South Wales
Australia	St John of God Hospital, Subiaco	Subiaco
Australia	Riverina Cancer Care Centre	Wagga Wagga
Belgium	ZNA Middelheim	Antwerp
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	AZ Groeninge	Kortrijk
Belgium	CHU Sart-Tilman	Liège
Belgium	Equipe de Recherche Clinique, Département d'Oncologie/Hématologie	Liège
Belgium	AZ DELTA	Roeselare
Canada	Juravinski Cancer Centre Hamilton Health Services	Hamilton	Ontario
Canada	London Health Science Center - Victoria Hospital	London	Ontario
Canada	The Ottawa Hospital	Ottawa	Ontario
Canada	Princess Margaret Hospital	Toronto
Denmark	Copenhagen University Hospital	Copenhagen
Denmark	Herlev Hospital	Herlev
Denmark	Vejle Sygehus	Vejle
France	Centre François Baclesse	Caen
France	Centre Georges François Leclerc	Dijon
France	Clinique Victor Hugo Centre Jean Bernard	Le Mans
France	Hôpital Privé La Louvière	Lille
France	Polyclinique de Gentilly (Centre D'Oncologie De Gentilly)	Nancy
France	Institut Curie	Paris
France	Hôpital Privé des Côtes d'Armor	Plérin
France	CRLCC Eugene Marquis	Rennes
Germany	Gemeinschaftspraxis fur Hamatologie & Onkologie	Augsburg
Germany	Charite Universitatsmedizin Berlin	Berlin
Germany	Universitatsklinikum Carl Gustav Carus	Dresden
Germany	Universitatsklinikum Dusseldorf	Dusseldorf
Germany	Urologische Gemeinschaftspraxis	Emmendingen
Germany	Universitaetsklinikum Hamburg-Eppendorf (UKE)	Hamburg
Germany	Universitaetsklinikum Heidelberg	Heidelberg
Germany	Universitatsklinikum Jena	Jena
Germany	Universitätsklinik Köln	Köln
Germany	Universitätsklinikum Schleswig-Holstein	Lübeck
Germany	Medizinischen Fakultät Mannheim der Universität Heidelberg	Mannheim
Germany	Studienpraxis Urologie	Nürtingen
Germany	University of Tuebingen	Tuebingen
Germany	Die Gesundhehitsunion DGU	Wuppertal
Ireland	Cork University Hospital	Cork
Ireland	Adelaide & Meath Hospital, Incorporating the National Children's Hospital	Dublin
Ireland	Mater Misericordiae University Hospital	Dublin
Ireland	St James's Hospital	Dublin
Ireland	St. Vincent's University Hospital	Dublin
Israel	Rambam Health Care Campus (RHCC), Rambam Medical Center	Haifa
Israel	Hadassah University Hospital	Jerusalem
Israel	Meir Medical Center	Kfar Saba
Israel	Rabin Medical Center-Beilinson Campus	Petach Tikva
Israel	Chaim Sheba Medical Center	Ramat Gan
Israel	The Tel Aviv Sourasky Medical Center (Ichilov Hospital)	Tel Aviv
Italy	Ospedale San Donato, Azienda USLSUDEST	Arezzo
Italy	Ospedale Santa Maria delle Croci	Faenza
Italy	IEO Instituto Europeo di Oncologia	Milano
Italy	IRCCS Istituto Nazionale dei Tumori (INT)	Milano
Italy	University of Modena and Reggio Emilia Medical Oncology	Modena
Italy	Azienda Ospedaliera San Camillo-Forlanini	Rome
Italy	Azienda Opsedaliera S. Maria di Terni	Terni
Italy	Santa Chiara Hospital, Dept Medical Oncology	Trento
Spain	Hospital Universitari Germans Trias i Pujol	Badalona
Spain	Hospital Clínic i Provincial de Barcelona-Oncology	Barcelona
Spain	Hospital del Mar, Servicio de Oncología	Barcelona
Spain	Hospital Universitari Germans Trias i Pujol	Barcelona
Spain	Instituto Catalan de Oncologia	Barcelona
Spain	Hospital General Universitario de Guadalajara	Guadalajara
Spain	Hospital Universitario Lucus Augusti.	Lugo
Spain	Hospital 12 de Octubre	Madrid
Spain	Hospital Puerta de Hierro-Majadahonda	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	MD Anderson Cancer Center - Madrid	Madrid
Spain	Hospital Universitario Central de Asturias	Oviedo
Spain	Corporacio Sanitaria Parc Tauli	Sabadell
Spain	Marques de Valdecilla University Hospital (HUMV)	Santander
Spain	Hospital Universitario Virgen del Rocío	Sevilla
Spain	Instituto Valenciano de Oncologia IVO	Valencia
United Kingdom	Oxford University Hospitals	Headington
United Kingdom	Royal Liverpool Hospital	Liverpool
United Kingdom	Guy's Hospital	London
United Kingdom	London Health Science Center - Victoria Hospital	London
United Kingdom	Sarah Cannon Research Institutute - UK	London
United Kingdom	Mount Vernon Cancer Centre	Northwood	England
United Kingdom	Wexham Park Hospital	Slough	Berkshire
United Kingdom	Southampton General Hospital	Southampton
United Kingdom	Royal Marsden Hospital	Sutton	Surrey
United Kingdom	Musgrove Park Hospital	Taunton
United Kingdom	The Clatterbridge Cancer Centre NHS Foundation Trust	Wirral
United States	VA Ann Arbor Healthcare System	Ann Arbor	Michigan
United States	Atlanta Urological Group	Atlanta	Georgia
United States	Rocky Mountain Cancer Centers	Aurora	Colorado
United States	University of Maryland Greenebaum Cancer Center	Baltimore	Maryland
United States	Walter Reed Hospital	Bethesda	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Boca Raton Community Hospital, Inc.	Boca Raton	Florida
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Roswell Park	Buffalo	New York
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	The Urology Group	Cincinnati	Ohio
United States	Carolina Urology Partners	Concord	North Carolina
United States	Texas Oncology Medical City Dallas	Dallas	Texas
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Henry Ford Hospital	Detroit	Michigan
United States	Fairview Hospital	Edina	Minnesota
United States	Florida Cancer Specialists	Fort Myers	Florida
United States	Consultants in Medical Oncology Hematology	Horsham	Pennsylvania
United States	UT Health Science Center	Houston	Texas
United States	HCA Midwest Division - Kansas City	Kansas City	Missouri
United States	Kettering Cancer Center	Kettering	Ohio
United States	Alliance Research Centers	Laguna Hills	California
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Premier Urology Associates dba/AdvanceMed Research	Lawrenceville	New Jersey
United States	University of Southern California	Los Angeles	California
United States	VA Greater Los Angeles Healthcare System	Los Angeles	California
United States	Clinical Research Solutions	Middleburg Heights	Ohio
United States	Minnesota Oncology Hematology, P.A.	Minneapolis	Minnesota
United States	Minnesota Veterans Research Institute	Minneapolis	Minnesota
United States	SCRI - Tennessee Oncology	Nashville	Tennessee
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Yale School of Medicine	New Haven	Connecticut
United States	Ochsner Medical Center	New Orleans	Louisiana
United States	Memorial Sloan Kettering CC	New York	New York
United States	NYU Perlmutter Cancer Center	New York	New York
United States	Weill Cornell Medical College/NewYork-Presbyterian Hospital	New York	New York
United States	4701 Ogletown Stanton Rd.	Newark	Delaware
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	Alegent Health Bergan Mercy Hospital , GU Research Network	Omaha	Nebraska
United States	Nebraska Cancer Specialists	Omaha	Nebraska
United States	University of Florida Health Cancer Center	Orlando	Florida
United States	Stanford University	Palo Alto	California
United States	Mayo Clinc	Phoenix	Arizona
United States	VA Portland Health Care System	Portland	Oregon
United States	Premier Medical Group of the Hudson Valley PC	Poughkeepsie	New York
United States	University of Rochester	Rochester	New York
United States	Sharp Memorial Hospital	San Diego	California
United States	Pacific Hematology Oncology Associates	San Francisco	California
United States	San Francisco VA Health Care System	San Francisco	California
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California
United States	Redwood Regional Medical Group	Santa Rosa	California
United States	VA Puget Sound	Seattle	Washington
United States	SUNY Upstate Medical University	Syracuse	New York
United States	Moffitt Cancer Center	Tampa	Florida
United States	Arizona Oncology Associates	Tucson	Arizona
United States	Texas Oncology - Tyler	Tyler	Texas
United States	Kaiser Permanente Medical Center (Vallejo)	Vallejo	California
United States	Georgetown University Medical Center	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
zr Pharma & GmbH	Foundation Medicine

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Denmark,  France,  Germany,  Ireland,  Israel,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Confirmed Objective Response Rate (ORR) by Gene in Patients With Measurable Disease at Baseline Per Central Independent Radiology Review (IRR)	The primary efficacy endpoint is confirmed radiographic ORR by central IRR. ORR is defined as the percentage of patients with a confirmed CR (complete response) or PR (partial response) by mRECIST (modified Response Evaluation Criteria in Solid Tumors) v1.1/PCWG3 (Prostate Cancer Working Group 3) criteria. The confirmed response is defined as a CR or PR on subsequent tumor assessment at least 28 days after first response documentation in the absence of confirmed progression in bone. CR is disappearance of all target and non-target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.	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	Confirmed Objective Response Rate (ORR) by Gene in Patients With Measurable Disease at Baseline Per Investigator (INV)	A supportive efficacy endpoint is confirmed radiographic ORR by INV. ORR is defined as the percentage of patients with a confirmed CR (complete response) or PR (partial response) by mRECIST (modified Response Evaluation Criteria in Solid Tumors) v1.1/PCWG3 (Prostate Cancer Working Group 3) criteria. The confirmed response is defined as a CR or PR on subsequent tumor assessment at least 28 days after first response documentation in the absence of confirmed progression in bone. CR is disappearance of all target and non-target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.	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	Duration of Response (DOR) by Gene in Patients With Confirmed Response Per Central Independent Radiology Review (IRR)	A secondary efficacy endpoint is DOR by central IRR. The DOR is defined as the time from the date that a confirmed response per modified RECIST Version 1.1/PCWG3 is first reported to the time that progressive disease (PD) is first documented. Progressive disease is defined using RECIST v1.1, as at least a 20% increase in the sum of the diameters of target lesions, or an unequivocal increase in non-target lesions, or the appearance of new lesions. PCWG3 criteria is used to document evidence of disease progression in bone lesions.	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	Duration of Response (DOR) by Gene in Patients With Confirmed Response Per Investigator	A secondary efficacy endpoint is DOR as assessed by the investigator. The DOR is defined as the time from the date that a confirmed response per modified RECIST Version 1.1/PCWG3 is first reported to the time that progressive disease (PD) is first documented. Progressive disease is defined using RECIST v1.1, as at least a 20% increase in the sum of the diameters of target lesions, or an unequivocal increase in non-target lesions, or the appearance of new lesions. PCWG3 criteria is used to document evidence of disease progression in bone lesions.	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	Confirmed PSA Response (= 50% Decrease) by Gene as Assessed by Local Laboratory	A secondary endpoint is confirmed PSA (prostate-specific antigen) response (= 50% reduction) as assessed by local laboratory. Confirmed PSA response is analyzed for all patients who had PSA value at baseline and is defined as the percentage of patients having 2 consecutive PSA values (at least 3 weeks apart) that are at least 50% lower than baseline and that occur prior to PSA progression. PSA progression is defined as a = 25% increase and absolute increase of = 2 ng/mL above the nadir in PSA.	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.
Secondary	Confirmed PSA Response (= 90% Decrease) by Gene as Assessed by Local Laboratory	A secondary endpoint is confirmed PSA (prostate-specific antigen) response (= 90% reduction) as assessed by local laboratory. Confirmed PSA response is analyzed for all patients who had PSA value at baseline and is defined as the percentage of patients having 2 consecutive PSA values (at least 3 weeks apart) that are at least 90% lower than baseline and that occur prior to PSA progression. PSA progression is defined as a = 25% increase and absolute increase of = 2 ng/mL above the nadir in PSA.	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.
Secondary	Radiologic Progression-free Survival (rPFS) by Gene in All Patients Per Central Independent Radiology Review (IRR)	A secondary efficacy endpoint is Radiologic Progression-free Survival (rPFS) assessed by IRR. rPFS is defined as the time from first dose of rucaparib to the date of first objective evidence of radiographic progression (soft tissue or bone lesion) or death due to any cause, whichever occurs first, plus 1 day. Radiographic disease progression includes confirmed bone disease progression and soft tissue disease progression adjudicated by IRR using the PCWG3 guidelines for bone disease and modified RECIST Version 1.1 for soft tissue disease.	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	Radiologic Progression-free Survival (rPFS) by Gene in All Patients Per Investigator	A secondary efficacy endpoint is Radiologic Progression-free Survival (rPFS) assessed by Investigator. rPFS is defined as the time from first dose of rucaparib to the date of first objective evidence of radiographic progression (soft tissue or bone lesion) or death due to any cause, whichever occurs first, plus 1 day. Radiographic disease progression includes confirmed bone disease progression and soft tissue disease progression using the PCWG3 guidelines for bone disease and modified RECIST Version 1.1 for soft tissue disease.	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	Overall Survival (OS) by Gene	A secondary efficacy endpoint is Overall Survival (OS). OS is defined as the date from first dose of rucaparib to the date of death due to any cause, +1 day.	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
Secondary	Clinical Benefit Rate (CBR) by Gene Per Central Independent Radiology Review (IRR)	A secondary efficacy endpoint is Clinical Benefit Rate (CBR) assessed by IRR. CBR is defined as the number of patients without radiographic progression (defined by modified RECIST Version 1.1/ PCWG3 criteria) who were continuing with study drug treatment through the given time interval divided by the number of patients who had the given amount of follow-up. Clinical benefit rates are summarized at 6 and 12 months.	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	Clinical Benefit Rate (CBR) by Gene Per Investigator	A secondary efficacy endpoint is Clinical Benefit Rate (CBR) assessed by Investigator. CBR is defined as the number of patients without radiographic progression (defined by modified RECIST Version 1.1/ PCWG3 criteria) who were continuing with study drug treatment through the given time interval divided by the number of patients who had the given amount of follow-up. Clinical benefit rates are summarized at 6 and 12 months.	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	Time to PSA Progression by Gene	A secondary efficacy endpoint is time to PSA progession. Time to PSA progression is defined as the time from first dose of rucaparib to the date that a = 25% increase and absolute increase of = 2 ng/mL above the nadir (or baseline if there was no PSA decline after baseline) in PSA was measured, plus 1 day. The increase must be confirmed by a second consecutive assessment conducted at least 3 weeks later (unless the PSA progression occurred at the last recorded PSA assessment). If confirmed, the date used for time of PSA progression is the earlier of the 2 PSA dates.	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.
Secondary	Steady State Trough (Cmin) Level Rucaparib Concentrations	Trough (Cmin) concentrations of rucaparib are summarized for all patients with at least one PK sample collected. The absolute values of rucaparib plasma concentration at each time point are presented by gene.	Participants were assessed at Study Day 29, Day 57, Day 85 and Day 113