A Study of Rucaparib in Patients With Metastatic Castration-resistant Prostate Cancer and Homologous Recombination Gene Deficiency
- Conditions
- Metastatic Castration Resistant Prostate Cancer
- Interventions
- Registration Number
- NCT02952534
- Lead Sponsor
- pharmaand GmbH
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 277
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Rucaparib Rucaparib Oral rucaparib (monotherapy)
- Primary Outcome Measures
Name Time Method Confirmed Objective Response Rate (ORR) by Gene in Patients With Measurable Disease at Baseline Per Central Independent Radiology Review (IRR) 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. 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.
- Secondary Outcome Measures
Name Time Method Duration of Response (DOR) by Gene in Patients With Confirmed Response Per Central Independent Radiology Review (IRR) 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. 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.
Confirmed Objective Response Rate (ORR) by Gene in Patients With Measurable Disease at Baseline Per Investigator (INV) 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. 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.
Confirmed PSA Response (≥ 90% Decrease) by Gene as Assessed by Local Laboratory 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. 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.
Radiologic Progression-free Survival (rPFS) by Gene in All Patients Per Central Independent Radiology Review (IRR) 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. 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.
Radiologic Progression-free Survival (rPFS) by Gene in All Patients Per Investigator 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. 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.
Clinical Benefit Rate (CBR) by Gene Per Central Independent Radiology Review (IRR) 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. 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.
Time to PSA Progression by Gene 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. 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.
Duration of Response (DOR) by Gene in Patients With Confirmed Response Per Investigator 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. 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.
Clinical Benefit Rate (CBR) by Gene Per Investigator 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. 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.
Steady State Trough (Cmin) Level Rucaparib Concentrations Participants were assessed at Study Day 29, Day 57, Day 85 and Day 113 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.
Confirmed PSA Response (≥ 50% Decrease) by Gene as Assessed by Local Laboratory 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. 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.
Overall Survival (OS) by Gene 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 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.
Trial Locations
- Locations (147)
Rutgers Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
University of Southern California
🇺🇸Los Angeles, California, United States
Atlanta Urological Group
🇺🇸Atlanta, Georgia, United States
University of Chicago Comprehensive Cancer Center
🇺🇸Chicago, Illinois, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Las Vegas, Nevada, United States
Minnesota Oncology Hematology, P.A.
🇺🇸Minneapolis, Minnesota, United States
Minnesota Veterans Research Institute
🇺🇸Minneapolis, Minnesota, United States
Premier Urology Associates dba/AdvanceMed Research
🇺🇸Lawrenceville, New Jersey, United States
4701 Ogletown Stanton Rd.
🇺🇸Newark, Delaware, 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
Alliance Research Centers
🇺🇸Laguna Hills, California, United States
Consultants in Medical Oncology Hematology
🇺🇸Horsham, Pennsylvania, United States
Boca Raton Community Hospital, Inc.
🇺🇸Boca Raton, Florida, United States
Clinical Research Solutions
🇺🇸Middleburg Heights, Ohio, United States
Roswell Park
🇺🇸Buffalo, New York, United States
The Urology Group
🇺🇸Cincinnati, Ohio, United States
VA Puget Sound
🇺🇸Seattle, Washington, United States
Virginia Oncology Associates
🇺🇸Norfolk, Virginia, United States
Memorial Sloan Kettering CC
🇺🇸New York, New York, United States
SUNY Upstate Medical University
🇺🇸Syracuse, New York, United States
Charite Universitatsmedizin Berlin
🇩🇪Berlin, Germany
Urologische Gemeinschaftspraxis
🇩🇪Emmendingen, Germany
Premier Medical Group of the Hudson Valley PC
🇺🇸Poughkeepsie, New York, United States
Cabrini Hospital
🇦🇺Malvern, Victoria, Australia
Cork University Hospital
🇮🇪Cork, Ireland
IEO Instituto Europeo di Oncologia
🇮🇹Milano, Italy
Azienda Opsedaliera S. Maria di Terni
🇮🇹Terni, Italy
Hospital Puerta de Hierro-Majadahonda
🇪🇸Madrid, Spain
Hospital Clínic i Provincial de Barcelona-Oncology
🇪🇸Barcelona, Spain
Hadassah University Hospital
🇮🇱Jerusalem, Israel
Texas Oncology Medical City Dallas
🇺🇸Dallas, Texas, United States
Marques de Valdecilla University Hospital (HUMV)
🇪🇸Santander, Spain
Universitaetsklinikum Heidelberg
🇩🇪Heidelberg, Germany
Universitatsklinikum Jena
🇩🇪Jena, Germany
Chaim Sheba Medical Center
🇮🇱Ramat Gan, Israel
Wexham Park Hospital
🇬🇧Slough, Berkshire, United Kingdom
Hospital Universitario Central de Asturias
🇪🇸Oviedo, Spain
Royal Liverpool Hospital
🇬🇧Liverpool, United Kingdom
Hospital Universitario Virgen del Rocío
🇪🇸Sevilla, Spain
UT Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Universitätsklinik Köln
🇩🇪Köln, Germany
Ospedale San Donato, Azienda USLSUDEST
🇮🇹Arezzo, Italy
Hospital Universitari Germans Trias i Pujol
🇪🇸Barcelona, Spain
Instituto Catalan de Oncologia
🇪🇸Barcelona, Spain
Mount Vernon Cancer Centre
🇬🇧Northwood, England, United Kingdom
Azienda Ospedaliera San Camillo-Forlanini
🇮🇹Rome, Italy
Hospital General Universitario de Guadalajara
🇪🇸Guadalajara, Spain
Sarah Cannon Research Institutute - UK
🇬🇧London, United Kingdom
Copenhagen University Hospital
🇩🇰Copenhagen, Denmark
St. Vincent's University Hospital
🇮🇪Dublin, Ireland
St James's Hospital
🇮🇪Dublin, Ireland
University of Rochester
🇺🇸Rochester, New York, United States
Mater Misericordiae University Hospital
🇮🇪Dublin, Ireland
Adelaide & Meath Hospital, Incorporating the National Children's Hospital
🇮🇪Dublin, Ireland
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Mayo Clinc
🇺🇸Phoenix, Arizona, United States
VA Portland Health Care System
🇺🇸Portland, Oregon, United States
Pacific Hematology Oncology Associates
🇺🇸San Francisco, California, United States
San Francisco VA Health Care System
🇺🇸San Francisco, California, United States
SCRI - Tennessee Oncology
🇺🇸Nashville, Tennessee, United States
Southampton General Hospital
🇬🇧Southampton, United Kingdom
Hôpital Privé des Côtes d'Armor
🇫🇷Plérin, France
Institut Curie
🇫🇷Paris, France
MD Anderson Cancer Center - Madrid
🇪🇸Madrid, Spain
Instituto Valenciano de Oncologia IVO
🇪🇸Valencia, Spain
Hospital Universitario Lucus Augusti.
🇪🇸Lugo, Spain
Hospital 12 de Octubre
🇪🇸Madrid, Spain
Die Gesundhehitsunion DGU
🇩🇪Wuppertal, Germany
Rocky Mountain Cancer Centers
🇺🇸Aurora, Colorado, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Walter Reed Hospital
🇺🇸Bethesda, Maryland, United States
Alegent Health Bergan Mercy Hospital , GU Research Network
🇺🇸Omaha, Nebraska, United States
Nebraska Cancer Specialists
🇺🇸Omaha, Nebraska, United States
Universitätsklinikum Schleswig-Holstein
🇩🇪Lübeck, Germany
VA Greater Los Angeles Healthcare System
🇺🇸Los Angeles, California, United States
Arizona Oncology Associates
🇺🇸Tucson, Arizona, United States
UCSF Helen Diller Family Comprehensive Cancer Center
🇺🇸San Francisco, California, United States
Sharp Memorial Hospital
🇺🇸San Diego, California, United States
Stanford University
🇺🇸Palo Alto, California, United States
Kaiser Permanente Medical Center (Vallejo)
🇺🇸Vallejo, California, United States
Redwood Regional Medical Group
🇺🇸Santa Rosa, California, United States
Georgetown University Medical Center
🇺🇸Washington, District of Columbia, United States
Yale School of Medicine
🇺🇸New Haven, Connecticut, United States
Florida Cancer Specialists
🇺🇸Fort Myers, Florida, United States
University of Florida Health Cancer Center
🇺🇸Orlando, Florida, United States
Ochsner Medical Center
🇺🇸New Orleans, Louisiana, United States
University of Maryland Greenebaum Cancer Center
🇺🇸Baltimore, Maryland, United States
Fairview Hospital
🇺🇸Edina, Minnesota, United States
VA Ann Arbor Healthcare System
🇺🇸Ann Arbor, Michigan, United States
HCA Midwest Division - Kansas City
🇺🇸Kansas City, Missouri, United States
Carolina Urology Partners
🇺🇸Concord, North Carolina, United States
Kettering Cancer Center
🇺🇸Kettering, Ohio, United States
UT Health Science Center
🇺🇸Houston, Texas, United States
Texas Oncology - Tyler
🇺🇸Tyler, Texas, United States
Royal Hobart Hospital
🇦🇺Hobart, Tasmania, Australia
Peninsula & Southeast Oncology
🇦🇺Frankston, Victoria, Australia
Northern Cancer Insitute, St. Leonards
🇦🇺Saint Leonards, New South Wales, Australia
Barwon Health, University Hospital Geelong
🇦🇺Geelong, Victoria, Australia
Southside Cancer Care Centre
🇦🇺Miranda, Australia
Orange Health Services
🇦🇺Orange, Australia
St John of God Hospital, Subiaco
🇦🇺Subiaco, Australia
Riverina Cancer Care Centre
🇦🇺Wagga Wagga, Australia
ZNA Middelheim
🇧🇪Antwerp, Belgium
Universitair Ziekenhuis Gent
🇧🇪Gent, Belgium
AZ Groeninge
🇧🇪Kortrijk, Belgium
Equipe de Recherche Clinique, Département d'Oncologie/Hématologie
🇧🇪Liège, Belgium
CHU Sart-Tilman
🇧🇪Liège, Belgium
AZ DELTA
🇧🇪Roeselare, Belgium
Juravinski Cancer Centre Hamilton Health Services
🇨🇦Hamilton, Ontario, Canada
Vejle Sygehus
🇩🇰Vejle, Denmark
The Ottawa Hospital
🇨🇦Ottawa, Ontario, Canada
London Health Science Center - Victoria Hospital
🇬🇧London, United Kingdom
Herlev Hospital
🇩🇰Herlev, Denmark
Princess Margaret Hospital
🇨🇦Toronto, Canada
Polyclinique de Gentilly (Centre D'Oncologie De Gentilly)
🇫🇷Nancy, France
Centre Georges François Leclerc
🇫🇷Dijon, France
Clinique Victor Hugo Centre Jean Bernard
🇫🇷Le Mans, France
Centre François Baclesse
🇫🇷Caen, France
Hôpital Privé La Louvière
🇫🇷Lille, France
Gemeinschaftspraxis fur Hamatologie & Onkologie
🇩🇪Augsburg, Germany
CRLCC Eugene Marquis
🇫🇷Rennes, France
Universitatsklinikum Carl Gustav Carus
🇩🇪Dresden, Germany
Universitatsklinikum Dusseldorf
🇩🇪Dusseldorf, Germany
Universitaetsklinikum Hamburg-Eppendorf (UKE)
🇩🇪Hamburg, Germany
Medizinischen Fakultät Mannheim der Universität Heidelberg
🇩🇪Mannheim, Germany
University of Tuebingen
🇩🇪Tuebingen, Germany
Studienpraxis Urologie
🇩🇪Nürtingen, Germany
Rambam Health Care Campus (RHCC), Rambam Medical Center
🇮🇱Haifa, Israel
Rabin Medical Center-Beilinson Campus
🇮🇱Petach Tikva, Israel
Meir Medical Center
🇮🇱Kfar Saba, Israel
The Tel Aviv Sourasky Medical Center (Ichilov Hospital)
🇮🇱Tel Aviv, Israel
Ospedale Santa Maria delle Croci
🇮🇹Faenza, Italy
IRCCS Istituto Nazionale dei Tumori (INT)
🇮🇹Milano, Italy
University of Modena and Reggio Emilia Medical Oncology
🇮🇹Modena, Italy
Santa Chiara Hospital, Dept Medical Oncology
🇮🇹Trento, Italy
Hospital del Mar, Servicio de Oncología
🇪🇸Barcelona, Spain
Hospital Universitario Ramón y Cajal
🇪🇸Madrid, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Corporacio Sanitaria Parc Tauli
🇪🇸Sabadell, Spain
Royal Marsden Hospital
🇬🇧Sutton, Surrey, United Kingdom
Oxford University Hospitals
🇬🇧Headington, United Kingdom
Musgrove Park Hospital
🇬🇧Taunton, United Kingdom
The Clatterbridge Cancer Centre NHS Foundation Trust
🇬🇧Wirral, United Kingdom
Guy's Hospital
🇬🇧London, United Kingdom