A Study of Rucaparib Versus Physician's Choice of Therapy in Participants With Metastatic Castration-resistant Prostate Cancer and Homologous Recombination Gene Deficiency
- Conditions
- Metastatic Castration Resistant Prostate Cancer
- Interventions
- Registration Number
- NCT02975934
- Lead Sponsor
- pharmaand GmbH
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 405
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Abiraterone acetate or Enzalutamide or Docetaxel Abiraterone acetate or Enzalutamide or Docetaxel Oral abiraterone acetate (monotherapy, given in combination with prednisone). Oral enzalutamide (monotherapy). Intravenous docetaxel (monotherapy, given in combination with prednisone or prednisolone). Rucaparib Rucaparib Oral rucaparib (monotherapy).
- Primary Outcome Measures
Name Time Method Radiographic Progression-free Survival (rPFS) by IRR in Participants With a BRCA or ATM Alteration Combined From enrollment to primary completion of study (Total follow-up was up to approximately 4 years) 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).Radiographic Progression-free Survival (rPFS) by IRR in Participants With a BRCA Alteration From enrollment to primary completion of study (Total follow-up was up to approximately 4 years) 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).
- Secondary Outcome Measures
Name Time Method Interim Overall Survival in Participants With a BRCA Alteration From enrollment to primary completion of study (up to approximately 5 years) 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.
Interim Overall Survival in Participants With a BRCA or ATM Alteration Combined From enrollment to primary completion of study (up to approximately 5 years) 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.
Objective Response Rate (ORR) by IRR in Participants With a BRCA Alteration From enrollment to primary completion of study (Total follow-up was up to approximately 4 years) 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.Objective Response Rate (ORR) by IRR in Participants With a BRCA or ATM Alteration Combined From enrollment to primary completion of study (Total follow-up was up to approximately 4 years) 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.Duration of Response (DOR) by IRR in Participants With a BRCA Alteration From enrollment to primary completion of study (Total follow-up was up to approximately 4 years) 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.
Duration of Response (DOR) by IRR in Participants With a BRCA or ATM Alteration Combined From enrollment to primary completion of study (Total follow-up was up to approximately 4 years) 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.
PSA Response in Participants With a BRCA Alteration From enrollment to primary completion of study (up to approximately 5 years) 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.
PSA Response in Participants With a BRCA or ATM Alteration Combined From enrollment to primary completion of study (up to approximately 5 years) 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.
Clinical Benefit Rate (CBR) by IRR at 6 Months in Participants With a BRCA Alteration From enrollment to 6 months 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.
Clinical Benefit Rate (CBR) by IRR at 6 Months in Participants With a BRCA or ATM Alteration Combined From enrollment to 6 months 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.
Time to Prostate Specific Antigen (PSA) Progression in Participants With a BRCA Alteration From enrollment to primary completion of study (up to approximately 5 years) 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.
Time to Prostate Specific Antigen (PSA) Progression in Participants With a BRCA or ATM Alteration Combined From enrollment to primary completion of study (up to approximately 5 years) 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.
Change in Patient-reported Outcome (PRO) in Participants With a BRCA Alteration: FACT-P From enrollment to up to approximately 25 weeks 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.
Change in Patient-reported Outcome (PRO) in Participants With a BRCA Alteration: BPI-SF From enrollment to up to approximately 25 weeks 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.
Change in Patient-reported Outcome (PRO) in Participants With a BRCA Alteration: EQ-5D-5L From enrollment to up to approximately 25 weeks 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.
Trough Plasma PK (Cmin) of Rucaparib Based on Sparse Sampling From enrollment to week 5 of dosing 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.
Trial Locations
- Locations (149)
Urology Clinics of North Texas
🇺🇸Dallas, Texas, United States
Texas Oncology Cancer Center-Round Rock
🇺🇸Round Rock, Texas, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
VA Puget Sound HCS
🇺🇸Seattle, Washington, United States
The Urology Group
🇺🇸Cincinnati, Ohio, United States
Urology of Virginia
🇺🇸Virginia Beach, Virginia, United States
Weill Cornell Medical College
🇺🇸New York, New York, United States
UT Health Science Center
🇺🇸Houston, Texas, United States
Atlanta Urological Group
🇺🇸Atlanta, Georgia, United States
Premier Urology Associates
🇺🇸Lawrenceville, New Jersey, United States
UT Southwestern Medical Center
🇺🇸Dallas, Texas, United States
SUNY Upstate Medical University
🇺🇸Syracuse, New York, United States
Maryland Oncology Hematology P.A.
🇺🇸Columbia, Maryland, United States
Carolina Urology Partners
🇺🇸Concord, North Carolina, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Las Vegas, Nevada, United States
Clinical Research Solutions
🇺🇸Middleburg Heights, Ohio, United States
Memorial Sloan Kettering CC
🇺🇸New York, New York, United States
NYU Perlmutter Cancer Center
🇺🇸New York, New York, United States
Hôpital Privé La Louvière
🇫🇷Lille, France
University Hospital Carl Gustav Carus
🇩🇪Dresden, Germany
Die GesundheitsUnion (DGU)
🇩🇪Wuppertal, Germany
Mater Misericordiae University Hospital
🇮🇪Dublin, Ireland
The Clatterbridge Cancer Centre NHS Foundation Trust
🇬🇧Wirral, United Kingdom
MD Anderson Cancer Center - Madrid
🇪🇸Madrid, Spain
University of Southern California
🇺🇸Beverly Hills, California, United States
St John of God Hospital, Subiaco
🇦🇺Subiaco, Western Australia, Australia
University of Rochester
🇺🇸Rochester, New York, United States
San Francisco VA Health Care System
🇺🇸San Francisco, California, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Minnesota Veterans Research Institute
🇺🇸Minneapolis, Minnesota, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Durham VA Medical Center
🇺🇸Durham, North Carolina, United States
Vejle Sygehus
🇩🇰Vejle, Denmark
Oxford Cancer Centre, Medical Oncology Unit
🇬🇧Oxford, England, United Kingdom
VA Portland Health Care System
🇺🇸Portland, Oregon, United States
Northwest Cancer Specialist DBA Compass Oncology
🇺🇸Portland, Oregon, United States
Knight Cancer Institute
🇺🇸Portland, Oregon, United States
The Ottawa Hospital
🇨🇦Ottawa, Ontario, Canada
Universitätsklinikum Schleswig-Holstein
🇩🇪Lubeck, Germany
Mayo Clinic - Rochester, MN
🇺🇸Rochester, Minnesota, United States
Alegent Health Bergan Mercy Hospital , GU Research Network
🇺🇸Omaha, Nebraska, United States
Nebraska Cancer Specialists
🇺🇸Omaha, Nebraska, United States
Rocky Mountain Cancer Centers
🇺🇸Aurora, Colorado, United States
Walter Reed National Military Medical Center
🇺🇸Bethesda, Maryland, United States
Hospital 12 de Octubre
🇪🇸Madrid, Spain
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Mayo Clinic - Arizona
🇺🇸Phoenix, Arizona, United States
VA Greater Los Angeles Healthcare System
🇺🇸Los Angeles, California, United States
Alliance Research Centers
🇺🇸Laguna Hills, California, 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
St. Joseph Heritage Healthcare
🇺🇸Santa Rosa, California, United States
UCSF Helen Diller Family Comprehensive Cancer Center
🇺🇸San Francisco, California, United States
Kaiser Permanente, Northern CA
🇺🇸Vallejo, California, United States
Boca Raton Community Hospital, Inc.
🇺🇸Boca Raton, Florida, United States
Medical Oncology Hematology Consultants - USOR
🇺🇸Newark, Delaware, United States
University of Maryland Greenebaum Cancer Center
🇺🇸Baltimore, Maryland, United States
Roswell Park
🇺🇸Buffalo, New York, United States
Premier Medical Group of the Hudson Valley PC
🇺🇸Poughkeepsie, New York, United States
Oncology Hematology Care
🇺🇸Cincinnati, Ohio, United States
Kettering Medical Center
🇺🇸Kettering, Ohio, United States
Urology Associates Clinical Research
🇺🇸Nashville, Tennessee, United States
Southside Cancer Care Centre
🇦🇺Miranda, New South Wales, Australia
University of Washington Fred Hutchinson Cancer Research Center
🇺🇸Seattle, Washington, United States
Orange Health Service
🇦🇺Orange, New South Wales, Australia
Peninsula & Southeast Oncology
🇦🇺Frankston, Australia
Barwon Health, University Hospital Geelong
🇦🇺Geelong, Australia
Riverina Cancer Care Centre
🇦🇺Wagga Wagga, Australia
Tom Baker Cancer Centre
🇨🇦Calgary, Alberta, Canada
CHU Sart-Tilman
🇧🇪Liège, Belgium
Centre Hospitalier Universitaire Dr-Georges-L.-Dumont
🇨🇦Moncton, New Brunswick, Canada
London Health Sciences Centre
🇨🇦London, Ontario, Canada
Lakeridge Health Medical Specialty Medical Oncology
🇨🇦Oshawa, Canada
Herlev Hospital
🇩🇰Herlev, Denmark
Centre Georges François Leclerc
🇫🇷Dijon, France
Sunnybrook Odette Cancer Centre
🇨🇦Toronto, Canada
Clinique Victor Hugo Centre Jean Bernard
🇫🇷Le Mans, France
Centre Léon Bérard
🇫🇷Lyon, France
Polyclinique de Gentilly (Centre D'Oncologie De Gentilly)
🇫🇷Nancy, France
Institut Curie
🇫🇷Paris, France
CRLCC Eugene Marquis
🇫🇷Rennes, France
Institut Gustave-Roussy
🇫🇷Villejuif, France
Charite - Universitaetsmedizin Berlin
🇩🇪Berlin, Germany
Centre Armoricain de Radiotherapie, Imagerie medicale et Oncologie, CARIO
🇫🇷Plérin, France
Gemeinschaftspraxis für Hämatologie&Onkologie
🇩🇪Augsburg, Germany
Universitatsklinikum Dusseldorf
🇩🇪Dusseldorf, Germany
Apotheke des Städtischen Klinikums Braunschweig
🇩🇪Braunschweig, Germany
Urologische Gemeinschaftspraxis
🇩🇪Emmendingen, Germany
Universitaetsklinikum Hamburg-Eppendorf (UKE)
🇩🇪Hamburg, Germany
Universitatsklinikum Jena
🇩🇪Jena, Germany
Universitätsklinikum Köln
🇩🇪Köln, Germany
Medizinischen Fakultät Mannheim der Universität Heidelberg
🇩🇪Mannheim, Germany
Studienpraxis Urologie
🇩🇪Nurtingen, Germany
Cork University Hospital
🇮🇪Cork, Ireland
University of Tuebingen
🇩🇪Tuebingen, Germany
Adelaide & Meath Hospital, Incorporating the National Children's Hospital
🇮🇪Dublin, Ireland
Mater Private Hospital (MPH)
🇮🇪Dublin, Ireland
St. Vincent's University Hospital
🇮🇪Dublin, Ireland
St James's Hospital
🇮🇪Dublin, Ireland
Rambam Health Care Campus (RHCC), Rambam Medical Center
🇮🇱Haifa, Israel
Meir Medical Center
🇮🇱Kfar Saba, Israel
The Tel Aviv Sourasky Medical Center (Ichilov Hospital)
🇮🇱Tel Aviv, Israel
Hadassah University Hospital
🇮🇱Jerusalem, Israel
Rabin Medical Center-Beilinson Campus
🇮🇱Petach Tikva, Israel
Chaim Sheba Medical Center
🇮🇱Tel Hashomer, Israel
Ospedale San Donato, Azienda USLSUDEST
🇮🇹Arezzo, Italy
Ospedale Santa Maria delle Croci
🇮🇹Faenza, Italy
IEO Instituto Europeo di Oncologia
🇮🇹Milano, Italy
Romagnolo per lo Studio e la Cura dei Tumori IRST-IRCCS - Oncologia medica
🇮🇹Meldola, Italy
University of Modena and Reggio Emilia
🇮🇹Modena, Italy
Presidio Ospedaliero Santa Chiara di Trento
🇮🇹Trento, Italy
Azienda Opsedaliera S. Maria di Terni
🇮🇹Terni, Italy
Azienda Ospedaliera San Camillo-Forlanini
🇮🇹Roma, Italy
Hospital Universitari Germans Trias i Pujol
🇪🇸Barcelona, Spain
Hospital Universitario Reina Sofia
🇪🇸Córdoba, Spain
Hospital Universitario Ramón y Cajal
🇪🇸Madrid, Spain
Hospital Universitario Lucus Augusti.
🇪🇸Lugo, Spain
Hospital Clinico Universitario Virgen de la Victoria
🇪🇸Málaga, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Universitario Central de Asturias
🇪🇸Oviedo, Spain
Corporacio Sanitaria Parc Tauli
🇪🇸Sabadell, Spain
Hospital Universitario Virgen del Rocío
🇪🇸Sevilla, Spain
Marques de Valdecilla University Hospital (HUMV)
🇪🇸Santander, Spain
Instituto Valenciano de Oncología
🇪🇸Valencia, Spain
Royal Marsden Hospital
🇬🇧London, United Kingdom
Royal Preston Hospital
🇬🇧Preston, England, United Kingdom
Wexham Park Hospital
🇬🇧Slough, England, United Kingdom
Velindre Hospital
🇬🇧Cardiff, United Kingdom
Musgrove Park Hospital
🇬🇧Taunton, United Kingdom
Royal Hobart Hospital
🇦🇺Hobart, Australia
Northern Cancer Insitute, St. Leonards
🇦🇺Saint Leonards, New South Wales, Australia
Arizona Oncology Associates - USOR
🇺🇸Tucson, Arizona, United States
Minnesota Oncology Hematology, P.A.
🇺🇸Minneapolis, Minnesota, United States
MultiCare Regional Cancer Center - Gig Harbor
🇺🇸Gig Harbor, Washington, United States
Copenhagen University Hospital
🇩🇰Copenhagen, Denmark
Cancer Care Manitoba
🇨🇦Winnipeg, Manitoba, Canada
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
Hospital General Universitario de Guadalajara
🇪🇸Guadalajara, Spain
Yale University School of Medicine
🇺🇸New Haven, Connecticut, United States
University of Florida Health Cancer Center
🇺🇸Orlando, Florida, United States
VA Ann Arbor Healthcare System
🇺🇸Ann Arbor, Michigan, United States
ZNA Middelheim
🇧🇪Antwerp, Belgium
AZ Groeninge
🇧🇪Kortrijk, Belgium
Clinique et Maternité Sainte-Elisabeth
🇧🇪Namur, Belgium
University of North Carolina Lineberger Cancer Center
🇺🇸Chapel Hill, North Carolina, United States
Kaiser Permanente Medical Group
🇺🇸Honolulu, Hawaii, United States
Ochsner Medical Center
🇺🇸New Orleans, Louisiana, United States
Guy's and St Thomas' NHS Foundation Trust
🇬🇧London, England, United Kingdom