A Study of Rucaparib Versus Physician's Choice of Therapy in Participants With Metastatic Castration-resistant Prostate Cancer and Homologous Recombination Gene Deficiency

Metastatic Castration Resistant Prostate Cancer Clinical Trial

— TRITON3  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02975934
• Other study ID #: CO-338-063
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 13, 2017
• Est. completion date: December 2024

Study information

• Verified date: March 2024
• Source: pharmaand GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 405
• Est. completion date: December 2024
• Est. primary completion date: August 25, 2022
• 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 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

Related Conditions & MeSH terms

• Metastatic Castration Resistant Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Rucaparib
Rucaparib will be administered daily.
• Abiraterone acetate or Enzalutamide or Docetaxel
Abiraterone acetate and enzalutamide will be administered daily. Docetaxel will be administered every 3 weeks.

Locations

Country	Name	City	State
Australia	Peninsula & Southeast Oncology	Frankston
Australia	Barwon Health, University Hospital Geelong	Geelong
Australia	Royal Hobart Hospital	Hobart
Australia	Southside Cancer Care Centre	Miranda	New South Wales
Australia	Orange Health Service	Orange	New South Wales
Australia	Northern Cancer Insitute, St. Leonards	Saint Leonards	New South Wales
Australia	St John of God Hospital, Subiaco	Subiaco	Western Australia
Australia	Riverina Cancer Care Centre	Wagga Wagga
Belgium	ZNA Middelheim	Antwerp
Belgium	AZ Groeninge	Kortrijk
Belgium	CHU Sart-Tilman	Liège
Belgium	Clinique et Maternité Sainte-Elisabeth	Namur
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	London Health Sciences Centre	London	Ontario
Canada	Centre Hospitalier Universitaire Dr-Georges-L.-Dumont	Moncton	New Brunswick
Canada	Lakeridge Health Medical Specialty Medical Oncology	Oshawa
Canada	The Ottawa Hospital	Ottawa	Ontario
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Canada	Sunnybrook Odette Cancer Centre	Toronto
Canada	Cancer Care Manitoba	Winnipeg	Manitoba
Denmark	Copenhagen University Hospital	Copenhagen
Denmark	Herlev Hospital	Herlev
Denmark	Vejle Sygehus	Vejle
France	Centre Georges François Leclerc	Dijon
France	Clinique Victor Hugo Centre Jean Bernard	Le Mans
France	Hôpital Privé La Louvière	Lille
France	Centre Léon Bérard	Lyon
France	Polyclinique de Gentilly (Centre D'Oncologie De Gentilly)	Nancy
France	Institut Curie	Paris
France	Centre Armoricain de Radiotherapie, Imagerie medicale et Oncologie, CARIO	Plérin
France	CRLCC Eugene Marquis	Rennes
France	Institut Gustave-Roussy	Villejuif
Germany	Gemeinschaftspraxis für Hämatologie&Onkologie	Augsburg
Germany	Charite - Universitaetsmedizin Berlin	Berlin
Germany	Apotheke des Städtischen Klinikums Braunschweig	Braunschweig
Germany	University Hospital Carl Gustav Carus	Dresden
Germany	Universitatsklinikum Dusseldorf	Dusseldorf
Germany	Urologische Gemeinschaftspraxis	Emmendingen
Germany	Universitaetsklinikum Hamburg-Eppendorf (UKE)	Hamburg
Germany	Universitatsklinikum Jena	Jena
Germany	Universitätsklinikum Köln	Köln
Germany	Universitätsklinikum Schleswig-Holstein	Lubeck
Germany	Medizinischen Fakultät Mannheim der Universität Heidelberg	Mannheim
Germany	Studienpraxis Urologie	Nurtingen
Germany	University of Tuebingen	Tuebingen
Germany	Die GesundheitsUnion (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	Mater Private Hospital (MPH)	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	The Tel Aviv Sourasky Medical Center (Ichilov Hospital)	Tel Aviv
Israel	Chaim Sheba Medical Center	Tel Hashomer
Italy	Ospedale San Donato, Azienda USLSUDEST	Arezzo
Italy	Ospedale Santa Maria delle Croci	Faenza
Italy	Romagnolo per lo Studio e la Cura dei Tumori IRST-IRCCS - Oncologia medica	Meldola
Italy	IEO Instituto Europeo di Oncologia	Milano
Italy	University of Modena and Reggio Emilia	Modena
Italy	Azienda Ospedaliera San Camillo-Forlanini	Roma
Italy	Azienda Opsedaliera S. Maria di Terni	Terni
Italy	Presidio Ospedaliero Santa Chiara di Trento	Trento
Spain	Hospital Universitari Germans Trias i Pujol	Barcelona
Spain	Hospital Universitario Reina Sofia	Córdoba
Spain	Hospital General Universitario de Guadalajara	Guadalajara
Spain	Hospital Universitario Lucus Augusti.	Lugo
Spain	Hospital 12 de Octubre	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	MD Anderson Cancer Center - Madrid	Madrid
Spain	Hospital Clinico Universitario Virgen de la Victoria	Málaga
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 Oncología	Valencia
United Kingdom	Velindre Hospital	Cardiff
United Kingdom	Guy's and St Thomas' NHS Foundation Trust	London	England
United Kingdom	Royal Marsden Hospital	London	England
United Kingdom	Royal Marsden Hospital	London
United Kingdom	Oxford Cancer Centre, Medical Oncology Unit	Oxford	England
United Kingdom	Royal Preston Hospital	Preston	England
United Kingdom	Wexham Park Hospital	Slough	England
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 National Military Medical Center	Bethesda	Maryland
United States	University of Southern California	Beverly Hills	California
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 North Carolina Lineberger Cancer Center	Chapel Hill	North Carolina
United States	Oncology Hematology Care	Cincinnati	Ohio
United States	The Urology Group	Cincinnati	Ohio
United States	Maryland Oncology Hematology P.A.	Columbia	Maryland
United States	Carolina Urology Partners	Concord	North Carolina
United States	Urology Clinics of North Texas	Dallas	Texas
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Henry Ford Hospital	Detroit	Michigan
United States	Durham VA Medical Center	Durham	North Carolina
United States	MultiCare Regional Cancer Center - Gig Harbor	Gig Harbor	Washington
United States	Kaiser Permanente Medical Group	Honolulu	Hawaii
United States	UT Health Science Center	Houston	Texas
United States	Kettering Medical 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	Lawrenceville	New Jersey
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	University of Minnesota	Minneapolis	Minnesota
United States	Urology Associates Clinical Research	Nashville	Tennessee
United States	Yale University 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	New York	New York
United States	Medical Oncology Hematology Consultants - USOR	Newark	Delaware
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	Mayo Clinic - Arizona	Phoenix	Arizona
United States	Knight Cancer Institute	Portland	Oregon
United States	Northwest Cancer Specialist DBA Compass Oncology	Portland	Oregon
United States	VA Portland Health Care System	Portland	Oregon
United States	Premier Medical Group of the Hudson Valley PC	Poughkeepsie	New York
United States	Mayo Clinic - Rochester, MN	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	Texas Oncology Cancer Center-Round Rock	Round Rock	Texas
United States	San Bernardino Urological Associates	San Bernardino	California
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	St. Joseph Heritage Healthcare	Santa Rosa	California
United States	University of Washington Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	VA Puget Sound HCS	Seattle	Washington
United States	SUNY Upstate Medical University	Syracuse	New York
United States	Arizona Oncology Associates - USOR	Tucson	Arizona
United States	Kaiser Permanente, Northern CA	Vallejo	California
United States	Urology of Virginia	Virginia Beach	Virginia

Sponsors (2)

Lead Sponsor	Collaborator
pharmaand GmbH	Foundation Medicine

Countries where clinical trial is conducted

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

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Radiographic Progression-free Survival (rPFS) by IRR in Participants With a BRCA Alteration	The primary efficacy endpoint for the study is rPFSirr, defined as the time from randomization to the first objective evidence of radiographic progression, or death due to any cause (whichever occurs first).; Radiographic disease progression includes confirmed soft tissue disease progression and confirmed bone disease progression as per modified RECIST Version 1.1 (at least a 20% increase in the sum of the LD of target lesions or appearance of one or more new extra-skeletal lesions and/or unequivocal progression of existing nontarget lesions) or PCWG3 criteria Progression by bone is determined by PCWG3 criteria in which at least two new lesions appearing during the first 12-week flare window followed by 2 additional new lesions in the confirmatory scan appearing after the 12-week flare window, or after the 12-week flare window, at least 2 new lesions relative to the first post-treatment scan confirmed on a subsequent scan).	From enrollment to primary completion of study (Total follow-up was up to approximately 4 years)
Primary	Radiographic Progression-free Survival (rPFS) by IRR in Participants With a BRCA or ATM Alteration Combined	The primary efficacy endpoint for the study is rPFSirr, defined as the time from randomization to the first objective evidence of radiographic progression, or death due to any cause (whichever occurs first).; Radiographic disease progression includes confirmed soft tissue disease progression and confirmed bone disease progression as per modified RECIST Version 1.1 (at least a 20% increase in the sum of the LD of target lesions or appearance of one or more new extra-skeletal lesions and/or unequivocal progression of existing nontarget lesions) or PCWG3 criteria (Progression by bone is determined by PCWG3 criteria in which at least two new lesions appearing during the first 12-week flare window followed by 2 additional new lesions in the confirmatory scan appearing after the 12-week flare window, or after the 12-week flare window, at least 2 new lesions relative to the first post-treatment scan confirmed on a subsequent scan).	From enrollment to primary completion of study (Total follow-up was up to approximately 4 years)
Secondary	Interim Overall Survival in Participants With a BRCA Alteration	Overall survival time is calculated as the time from randomization to death (by any cause) +1 day. Participants who have not died will be censored on the date the participant was last known to be alive.	From enrollment to primary completion of study (up to approximately 5 years)
Secondary	Interim Overall Survival in Participants With a BRCA or ATM Alteration Combined	Overall survival time is calculated as the time from randomization to death (by any cause) +1 day. Participants who have not died will be censored on the date the participants was last known to be alive.	From enrollment to primary completion of study (up to approximately 5 years)
Secondary	Objective Response Rate (ORR) by IRR in Participants With a BRCA Alteration	ORR is defined as the percentage of participants with a confirmed best response of Complete response (CR) or Partial Response (PR) in participants with measurable disease at study entry. Modified RECIST Version 1.1 criteria is used to determine ORR (ie, CR or PR by IRR assessment and no progression in bone per PCWG3 by IRR assessment).; 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.	From enrollment to primary completion of study (Total follow-up was up to approximately 4 years)
Secondary	Objective Response Rate (ORR) by IRR in Participants With a BRCA or ATM Alteration Combined	ORR is defined as the percentage of participants with a confirmed best response of Complete response (CR) or Partial Response (PR) in participants with measurable disease at study entry. Modified RECIST Version 1.1 criteria is used to determine ORR (ie, CR or PR by IRR assessment and no progression in bone per PCWG3 by IRR assessment).; 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.	From enrollment to primary completion of study (Total follow-up was up to approximately 4 years)
Secondary	Duration of Response (DOR) by IRR in Participants With a BRCA Alteration	DOR is defined as the time from the first confirmed response (CR or PR by modified RECIST Version 1.1 in participants with nodal or visceral ± nodal disease) until the first date that Progressive Disease (PD) (using the same criteria) is documented.	From enrollment to primary completion of study (Total follow-up was up to approximately 4 years)
Secondary	Duration of Response (DOR) by IRR in Participants With a BRCA or ATM Alteration Combined	DOR is defined as the time from the first confirmed response (CR or PR by modified RECIST Version 1.1 in participants with nodal or visceral ± nodal disease) until the first date that Progressive Disease (PD) (using the same criteria) is documented.	From enrollment to primary completion of study (Total follow-up was up to approximately 4 years)
Secondary	PSA Response in Participants With a BRCA Alteration	Confirmed PSA response is defined as = 50% reduction in PSA from baseline on at least two assessments conducted at least 3 weeks apart. PSA response is calculated for all participants with PSA values at baseline and at least one post-baseline assessment. PSA is assessed by a local laboratory.	From enrollment to primary completion of study (up to approximately 5 years)
Secondary	PSA Response in Participants With a BRCA or ATM Alteration Combined	Confirmed PSA response is defined as = 50% reduction in PSA from baseline on at least two assessments conducted at least 3 weeks apart. PSA response is calculated for all participants with PSA values at baseline and at least one post-baseline assessment. PSA is assessed by a local laboratory.	From enrollment to primary completion of study (up to approximately 5 years)
Secondary	Clinical Benefit Rate (CBR) by IRR at 6 Months in Participants With a BRCA Alteration	Defined as the percentage of participants with a complete response (CR), partial response (PR), and stable disease (SD) according to modified RECIST Version 1.1 with no progression in bone per PCWG3 criteria.	From enrollment to 6 months
Secondary	Clinical Benefit Rate (CBR) by IRR at 6 Months in Participants With a BRCA or ATM Alteration Combined	Defined as the percentage of participants with a Complete Response (CR), Partial Response (PR), and Stable Disease (SD), according to Modified RECIST Version 1.1 with no progression in bone per PCWG3 Criteria.	From enrollment to 6 months
Secondary	Time to Prostate Specific Antigen (PSA) Progression in Participants With a BRCA Alteration	Time to PSA progression is defined as the time from randomization to the date that a = 25% increase and absolute increase of = 2 ng/mL above the nadir (or baseline value for participants who did not have a decline in PSA) in PSA was measured. The increase must be confirmed by a second consecutive assessment conducted at least 3 weeks later.	From enrollment to primary completion of study (up to approximately 5 years)
Secondary	Time to Prostate Specific Antigen (PSA) Progression in Participants With a BRCA or ATM Alteration Combined	Time to PSA progression is defined as the time from randomization to the date that a = 25% increase and absolute increase of = 2 ng/mL above the nadir (or baseline value for participants who did not have a decline in PSA) in PSA was measured. The increase must be confirmed by a second consecutive assessment conducted at least 3 weeks later.	From enrollment to primary completion of study (up to approximately 5 years)
Secondary	Change in Patient-reported Outcome (PRO) in Participants With a BRCA Alteration: FACT-P	Changes in health and pain status from baseline to week 25 using: Functional Assessment of Cancer Therapy-Prostate questionnaire (FACT-P total score, on a scale of 0 to 156 where a higher score is better quality of life). The greater the decrease in score (ie more negative) from baseline to week 25 the greater the decrease in health status. Assessments completed during screening, at study treatment visits (Day 1, Day 15, Day 29, Day 43, Day 57, and every 29 days thereafter) (during the Treatment Phase, the Treatment Discontinuation Visit, and during the Follow-up Phase.	From enrollment to up to approximately 25 weeks
Secondary	Change in Patient-reported Outcome (PRO) in Participants With a BRCA Alteration: BPI-SF	Changes in health and pain status from baseline to week 25 using: Brief Pain Inventory-Short Form (BPI-SF) questionnaire (on a scale of 1 to 10, from mild to severe, for pain and pain-interference scores). A decrease indicates less severe pain/interference. Assessments completed during screening, at study treatment visits (Day 1, Day 15, Day 29, Day 43, Day 57, and every 29 days thereafter) (during the Treatment Phase, the Treatment Discontinuation Visit, and during the Follow-up Phase.	From enrollment to up to approximately 25 weeks
Secondary	Change in Patient-reported Outcome (PRO) in Participants With a BRCA Alteration: EQ-5D-5L	Changes in health and pain status from baseline to week 25 using: EuroQol-5D-5L Visual Analogue Scale (EQ-5D-5L VAS; on a scale from 100 to 0, from best to worst health status). The greater the increase in score (including more negative) from baseline to week 25 the greater the increase in health status. Assessments completed during screening, at study treatment visits (Day 1, Day 15, Day 29, Day 43, Day 57, and every 29 days thereafter) during the Treatment Phase, the Treatment Discontinuation Visit, and during the Follow-up Phase.	From enrollment to up to approximately 25 weeks
Secondary	Trough Plasma PK (Cmin) of Rucaparib Based on Sparse Sampling	Mean trough PK plasma concentration over time in the safety population with at least one PK sample collected at timepoints week 5, 9, 13 and 17; only Week 5 data presented.	From enrollment to week 5 of dosing