A Clinical Study Evaluating The Benefit of Adding Rucaparib to Enzalutamide for Men With Metastatic Prostate Cancer That Has Become Resistant To Testosterone-Deprivation Therapy (CASPAR)
Castration-Resistant Prostate Carcinoma, Metastatic Prostate Adenocarcinoma, Stage IV Prostate Cancer AJCC v8
About this trial
This is an interventional treatment trial for Castration-Resistant Prostate Carcinoma
Eligibility Criteria
Inclusion Criteria:
- Histologic/cytologic documentation of prostate adenocarcinoma
- Adequate archival tumor specimen or archival slides must be available to be tested as part of the trial screening (most recent metastatic site biopsy preferred, but primary prostate biopsy allowed if metastatic biopsy is not available or inadequate. A new biopsy is not required for pre-registration in the trial as long as sufficient archival tissue is available). Due to significant variability between tests, results from an existing targeted next-generation exome sequencing test may not be used for this trial
Progressive disease must be demonstrated at study entry while the patient is on continuous androgen deprivation therapy (ADT) or status post orchiectomy. Progressive disease is defined as one or more of the following criteria:
- PSA progression, defined by at least 2 consecutive rising PSA values at a minimum of 1-week intervals with the most recent PSA value being 1.0 ng/mL or higher, if confirmed PSA rise is the only indication of progression. Patients who received an anti-androgen must have PSA progression after withdrawal of anti-androgen therapy (>=4 weeks since last flutamide, bicalutamide or nilutamide, apalutamide or darolutamide)
- Radiographic progression per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for soft tissue lesions
- Bone metastasis progression per Prostate Cancer Working Group 3 (PCWG3) criteria
- Measurable or non-measurable metastatic disease
- No prior therapy for metastatic castration-resistant prostate cancer, defined as a treatment given for prostate cancer with radiographically-detectable metastasis and a serum testosterone level less than 50 ng/dl (1.73 nmol/L) at the time of registration
- >= 2 weeks or 5 half-lives (whichever is shorter) since prior therapy with flutamide, dutasteride, bicalutamide, niltamide, finasteride, aminoglutethimide, estrogens, cytoproterone, chemotherapy, abiraterone, apalutamide, or darolutamide
- >= 4 weeks or 5 half-lives (whichever is shorter) since any prior investigational therapy
- >= 4 weeks since a major surgery or radiation
- No prior therapy with enzalutamide, rucaparib or any other PARP inhibitor, or platinum chemotherapy
- Prior docetaxel and/or novel anti-androgen use is allowed only if given in the hormone-sensitive non-metastatic or metastatic, or castration-resistant non-metastatic disease setting
- Patient must have discontinued all previous treatments for cancer (except ADT and bone anti-responsive therapies such as denosumab or zoledronic acid) and must have recovered from all acute side effects of prior therapy or surgical procedures to =< grade 1 or baseline prior to randomization, with the exception of fatigue, alopecia or peripheral neuropathy
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Absolute neutrophil count (ANC) >= 1,500/mm^3
- Platelet count >= 100,000/mm^3
- Hemoglobin >= 10 g/dL
- Serum testosterone =< 50 ng/dl (=< 1.73 nmol/L)
- Serum creatinine =< 1.5 x upper limit of normal (ULN)
- Total bilirubin =< 1.5 x upper limit of normal (ULN)
- Aspartate transaminase (AST)/alanine transferase (ALT) =< 2.5 x upper limit of normal (ULN)
- No clinically suspected central nervous system (CNS) (leptomeningeal or parenchymal) metastases. Patients with a history of CNS metastasis(s) will be allowed as long (1) as the metastatic site(s) were adequately treated as demonstrated by clinical and radiographic improvement, AND (2) the patient has recovered from the intervention (no residual adverse events > Common Terminology Criteria for Adverse Events [CTCAE] grade 1), AND (3) the patient has remained without occurrence of new or worsening CNS symptoms for a period of 28 days prior to pre-registration
- No known or suspected history of cytopenia (low white blood cell [WBC], hemoglobin or platelet count) of greater than 3 months duration with an unknown cause, myelodysplastic syndrome, or hematologic malignancies
- No blood product transfusion, granulocyte/granulocyte-macrophage-colony stimulating factor (G-CSF/GM-CSF), or erythropoietin/thrombopoietin use within 14 days of pre-registration
- No history of syncope of cardiovascular etiology, uncontrolled cardiac arrhythmia, history of Mobitz II second degree or third degree heart block without a permanent pacemaker in place, myocardial ischemia or infarction, severe or unstable angina, New York Heart Association (NYHA) class II to IV heart failure, or stroke/transient ischemic attack (TIA) within the past 3 months
- No history of seizure or any condition that may increase the patient's seizure risk (e.g., prior cortical stroke, significant brain trauma) within 2 years
- No clinically active or chronic liver disease resulting in moderate/severe hepatic impairment (Child-Pugh class B or C), ascites, coagulopathy or bleeding due to liver dysfunction
- No clinical, laboratory or radiographic evidence of an active bacterial, fungal, or viral infection requiring treatment at the time of registration
- No planned palliative procedures for alleviation of bone pain such as radiation therapy or surgery
- No untreated spinal cord compression or evidence of spinal metastases with a risk of impending fracture or spinal cord compression
- No known or suspected contraindications or hypersensitivity to enzalutamide, rucaparib, or to any of the excipients
- No known or suspected gastrointestinal disorder affecting absorption of oral medications
- No prior malignancy for which the last treatment was given within the past 2 years, or any active concurrent malignancy with the exception of non-melanomatous localized skin cancers (such as squamous or basal cell carcinoma of the skin)
- Any concomitant medications that are strong inhibitors of CYP2C8 or inducers of CYP3A4 cytochrome enzymes must be discontinued prior to registration. Dose adjustments per Food and Drug Administration (FDA) label or clinical judgement should be considered for any concomitant medications that are moderate inhibitors of CYP2C8 or inducers of CYP3A4 cytochrome enzymes
- Any concomitant medications that are substrates of CYP3A4, CYP2C9 and CYP2C19 cytochrome enzymes should be monitored closely per clinical judgement of the treating physician
Sites / Locations
- Anchorage Associates in Radiation Medicine
- Anchorage Radiation Therapy Center
- Alaska Breast Care and Surgery LLC
- Alaska Oncology and Hematology LLC
- Alaska Women's Cancer Care
- Anchorage Oncology Centre
- Katmai Oncology Group
- Providence Alaska Medical Center
- Cancer Center at Saint Joseph's
- CHI Saint Vincent Cancer Center Hot Springs
- Kaiser Permanente-Deer Valley Medical Center
- Mission Hope Medical Oncology - Arroyo Grande
- Providence Saint Joseph Medical Center/Disney Family Cancer Center
- Kaiser Permanente Dublin
- Kaiser Permanente-Fremont
- Kaiser Permanente-Fresno
- Kaiser Permanente-Modesto
- Kaiser Permanente-Oakland
- Kaiser Permanente-Richmond
- Kaiser Permanente-Roseville
- Kaiser Permanente Downtown Commons
- Kaiser Permanente-South Sacramento
- Saint Helena Hospital
- Sharp Memorial Hospital
- Kaiser Permanente-San Francisco
- Kaiser Permanente-Santa Teresa-San Jose
- Kaiser Permanente San Leandro
- Pacific Central Coast Health Center-San Luis Obispo
- Kaiser San Rafael-Gallinas
- Kaiser Permanente Medical Center - Santa Clara
- Mission Hope Medical Oncology - Santa Maria
- Kaiser Permanente-Santa Rosa
- Kaiser Permanente-South San Francisco
- Kaiser Permanente-Stockton
- Northbay Cancer Center
- Kaiser Permanente Medical Center-Vacaville
- Kaiser Permanente-Vallejo
- Kaiser Permanente-Walnut Creek
- Penrose-Saint Francis Healthcare
- Rocky Mountain Cancer Centers-Penrose
- Porter Adventist Hospital
- Mercy Medical Center
- Southwest Oncology PC
- Saint Anthony Hospital
- Littleton Adventist Hospital
- Longmont United Hospital
- Rocky Mountain Cancer Centers-Longmont
- Parker Adventist Hospital
- Saint Mary Corwin Medical Center
- Veterans Affairs Connecticut Healthcare System-West Haven Campus
- MedStar Washington Hospital Center
- George Washington University Medical Center
- Mount Sinai Comprehensive Cancer Center at Aventura
- Holy Cross Hospital
- Mount Sinai Medical Center
- Augusta Oncology Associates PC-D'Antignac
- Augusta Oncology Associates PC-Wheeler
- Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
- Pali Momi Medical Center
- Hawaii Cancer Care Inc - Waterfront Plaza
- Queen's Cancer Cenrer - POB I
- Queen's Medical Center
- Straub Clinic and Hospital
- Queen's Cancer Center - Kuakini
- Kaiser Permanente Moanalua Medical Center
- Saint Alphonsus Cancer Care Center-Boise
- Saint Luke's Cancer Institute - Boise
- Saint Alphonsus Cancer Care Center-Caldwell
- Kootenai Health - Coeur d'Alene
- Walter Knox Memorial Hospital
- Saint Luke's Cancer Institute - Fruitland
- Idaho Urologic Institute-Meridian
- Saint Luke's Cancer Institute - Meridian
- Saint Luke's Cancer Institute - Nampa
- Saint Alphonsus Cancer Care Center-Nampa
- Kootenai Clinic Cancer Services - Post Falls
- Kootenai Cancer Clinic
- Saint Luke's Cancer Institute - Twin Falls
- Rush - Copley Medical Center
- Illinois CancerCare-Bloomington
- Loyola Center for Health at Burr Ridge
- Illinois CancerCare-Canton
- Memorial Hospital of Carbondale
- SIH Cancer Institute
- Illinois CancerCare-Carthage
- Centralia Oncology Clinic
- Northwestern University
- Rush University Medical Center
- University of Illinois
- Advocate Illinois Masonic Medical Center
- Carle at The Riverfront
- Cancer Care Specialists of Illinois - Decatur
- Decatur Memorial Hospital
- Northwestern Medicine Cancer Center Kishwaukee
- Illinois CancerCare-Dixon
- Carle Physician Group-Effingham
- Crossroads Cancer Center
- Illinois CancerCare-Eureka
- Illinois CancerCare-Galesburg
- Western Illinois Cancer Treatment Center
- Northwestern Medicine Cancer Center Delnor
- Ingalls Memorial Hospital
- Loyola Medicine Homer Glen
- Illinois CancerCare-Kewanee Clinic
- Northwestern Medicine Lake Forest Hospital
- Illinois CancerCare-Macomb
- Carle Physician Group-Mattoon/Charleston
- Loyola University Medical Center
- Marjorie Weinberg Cancer Center at Loyola-Gottlieb
- Cancer Care Center of O'Fallon
- Illinois CancerCare-Ottawa Clinic
- Advocate Lutheran General Hospital
- Illinois CancerCare-Pekin
- Illinois CancerCare-Peoria
- Methodist Medical Center of Illinois
- Illinois CancerCare-Peru
- Valley Radiation Oncology
- Illinois CancerCare-Princeton
- West Suburban Medical Center
- Southern Illinois University School of Medicine
- Springfield Clinic
- Memorial Medical Center
- Carle Cancer Center
- The Carle Foundation Hospital
- Northwestern Medicine Cancer Center Warrenville
- Illinois CancerCare - Washington
- Rush-Copley Healthcare Center
- Reid Health
- Memorial Hospital of South Bend
- Mary Greeley Medical Center
- McFarland Clinic - Ames
- McFarland Clinic - Boone
- Saint Anthony Regional Hospital
- Medical Oncology and Hematology Associates-West Des Moines
- Mercy Cancer Center-West Lakes
- Alegent Health Mercy Hospital
- Greater Regional Medical Center
- Iowa Methodist Medical Center
- Medical Oncology and Hematology Associates-Des Moines
- Broadlawns Medical Center
- Mercy Medical Center - Des Moines
- Mission Cancer and Blood - Laurel
- Iowa Lutheran Hospital
- McFarland Clinic - Trinity Cancer Center
- Trinity Regional Medical Center
- McFarland Clinic - Jefferson
- McFarland Clinic - Marshalltown
- Methodist West Hospital
- Mercy Medical Center-West Lakes
- Flaget Memorial Hospital
- Commonwealth Cancer Center-Corbin
- Saint Joseph Radiation Oncology Resource Center
- Saint Joseph Hospital East
- Saint Joseph London
- Jewish Hospital
- Saints Mary and Elizabeth Hospital
- UofL Health Medical Center Northeast
- Jewish Hospital Medical Center South
- Harold Alfond Center for Cancer Care
- Hickman Cancer Center
- Saint Joseph Mercy Hospital
- Bronson Battle Creek
- Saint Joseph Mercy Brighton
- Trinity Health IHA Medical Group Hematology Oncology - Brighton
- Saint Joseph Mercy Canton
- Trinity Health IHA Medical Group Hematology Oncology - Canton
- Caro Cancer Center
- Saint Joseph Mercy Chelsea
- Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
- Hematology Oncology Consultants-Clarkston
- Newland Medical Associates-Clarkston
- Ascension Saint John Hospital
- Great Lakes Cancer Management Specialists-Doctors Park
- Genesee Cancer and Blood Disease Treatment Center
- Genesee Hematology Oncology PC
- Genesys Hurley Cancer Institute
- Hurley Medical Center
- Spectrum Health at Butterworth Campus
- Trinity Health Grand Rapids Hospital
- Academic Hematology Oncology Specialists
- Great Lakes Cancer Management Specialists-Van Elslander Cancer Center
- Michigan Breast Specialists-Grosse Pointe Woods
- Bronson Methodist Hospital
- West Michigan Cancer Center
- Ascension Borgess Cancer Center
- Sparrow Hospital
- Hope Cancer Clinic
- Trinity Health Saint Mary Mercy Livonia Hospital
- Great Lakes Cancer Management Specialists-Macomb Medical Campus
- Michigan Breast Specialists-Macomb Township
- Saint Mary's Oncology/Hematology Associates of Marlette
- Toledo Clinic Cancer Centers-Monroe
- Trinity Health Muskegon Hospital
- Cancer and Hematology Centers of Western Michigan - Norton Shores
- 21st Century Oncology-Pontiac
- Hope Cancer Center
- Newland Medical Associates-Pontiac
- Saint Joseph Mercy Oakland
- Spectrum Health Reed City Hospital
- Ascension Saint Mary's Hospital
- Oncology Hematology Associates of Saginaw Valley PC
- Marie Yeager Cancer Center
- Bhadresh Nayak MD PC-Sterling Heights
- Ascension Saint Joseph Hospital
- Munson Medical Center
- Advanced Breast Care Center PLLC
- Great Lakes Cancer Management Specialists-Macomb Professional Building
- Macomb Hematology Oncology PC
- Michigan Breast Specialists-Warren
- Saint John Macomb-Oakland Hospital
- Saint Mary's Oncology/Hematology Associates of West Branch
- University of Michigan Health - West
- Huron Gastroenterology PC
- Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
- Sanford Joe Lueken Cancer Center
- Essentia Health Saint Joseph's Medical Center
- Mercy Hospital
- Essentia Health - Deer River Clinic
- Essentia Health Cancer Center
- Saint Luke's Hospital of Duluth
- Unity Hospital
- Essentia Health Hibbing Clinic
- Hennepin County Medical Center
- Minneapolis VA Medical Center
- Coborn Cancer Center at Saint Cloud Hospital
- Park Nicollet Clinic - Saint Louis Park
- Essentia Health Sandstone
- Sanford Thief River Falls Medical Center
- Essentia Health Virginia Clinic
- Sanford Cancer Center Worthington
- Saint Francis Medical Center
- Southeast Cancer Center
- MU Health - University Hospital/Ellis Fischel Cancer Center
- Parkland Health Center - Farmington
- Capital Region Southwest Campus
- Missouri Baptist Medical Center
- Mercy Hospital Saint Louis
- Sainte Genevieve County Memorial Hospital
- Missouri Baptist Sullivan Hospital
- Missouri Baptist Outpatient Center-Sunset Hills
- Community Hospital of Anaconda
- Billings Clinic Cancer Center
- Bozeman Deaconess Hospital
- Benefis Healthcare- Sletten Cancer Institute
- Great Falls Clinic
- Kalispell Regional Medical Center
- Saint Patrick Hospital - Community Hospital
- Community Medical Hospital
- CHI Health Saint Francis
- CHI Health Good Samaritan
- Saint Elizabeth Regional Medical Center
- Alegent Health Immanuel Medical Center
- Alegent Health Bergan Mercy Medical Center
- Alegent Health Lakeside Hospital
- Creighton University Medical Center
- Midlands Community Hospital
- OptumCare Cancer Care at Charleston
- OptumCare Cancer Care at Fort Apache
- New Hampshire Oncology Hematology PA-Concord
- Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
- Solinsky Center for Cancer Care
- Hackensack University Medical Center
- Saint Joseph's Regional Medical Center
- University of New Mexico Cancer Center
- Presbyterian Kaseman Hospital
- Presbyterian Rust Medical Center/Jorgensen Cancer Center
- Montefiore Medical Center-Einstein Campus
- Montefiore Medical Center-Weiler Hospital
- Montefiore Medical Center - Moses Campus
- The New York Hospital Medical Center of Queens
- Glens Falls Hospital
- Queens Hospital Center
- NYP/Weill Cornell Medical Center
- Nyack Hospital
- Wake Forest University at Clemmons
- Southeastern Medical Oncology Center-Clinton
- Southeastern Medical Oncology Center-Goldsboro
- Southeastern Medical Oncology Center-Jacksonville
- Wake Forest Baptist Health - Wilkes Medical Center
- Wake Forest University Health Sciences
- Sanford Bismarck Medical Center
- Essentia Health Cancer Center-South University Clinic
- Sanford South University Medical Center
- Southpointe-Sanford Medical Center Fargo
- Sanford Medical Center Fargo
- Sanford Broadway Medical Center
- Sanford Roger Maris Cancer Center
- Dayton Physicians LLC-Miami Valley South
- Miami Valley Hospital South
- Good Samaritan Hospital - Cincinnati
- Bethesda North Hospital
- TriHealth Cancer Institute-Westside
- TriHealth Cancer Institute-Anderson
- Cleveland Clinic Foundation
- Ohio State University Comprehensive Cancer Center
- Miami Valley Hospital
- Dayton Physician LLC-Miami Valley Hospital North
- Miami Valley Hospital North
- Armes Family Cancer Center
- Dayton Physicians LLC-Atrium
- Greater Dayton Cancer Center
- Kettering Medical Center
- Springfield Regional Cancer Center
- ProMedica Flower Hospital
- Mercy Health - Saint Anne Hospital
- Toledo Clinic Cancer Centers-Toledo
- Cancer Centers of Southwest Oklahoma Research
- University of Oklahoma Health Sciences Center
- Oklahoma Cancer Specialists and Research Institute-Tulsa
- Saint Alphonsus Medical Center-Baker City
- Saint Charles Health System
- Clackamas Radiation Oncology Center
- Providence Cancer Institute Clackamas Clinic
- Bay Area Hospital
- Providence Newberg Medical Center
- Saint Alphonsus Medical Center-Ontario
- Providence Portland Medical Center
- Providence Saint Vincent Medical Center
- Saint Charles Health System-Redmond
- Lehigh Valley Hospital-Cedar Crest
- Lehigh Valley Hospital - Muhlenberg
- Pocono Medical Center
- Lehigh Valley Hospital-Hazleton
- Thomas Jefferson University Hospital
- Guthrie Medical Group PC-Robert Packer Hospital
- Saint Joseph's/Candler - Bluffton Campus
- Prisma Health Cancer Institute - Spartanburg
- Prisma Health Cancer Institute - Easley
- Prisma Health Cancer Institute - Butternut
- Prisma Health Cancer Institute - Faris
- Prisma Health Greenville Memorial Hospital
- Prisma Health Cancer Institute - Eastside
- Prisma Health Cancer Institute - Greer
- South Carolina Cancer Specialists PC
- Prisma Health Cancer Institute - Seneca
- Avera Cancer Institute-Aberdeen
- Sanford Cancer Center Oncology Clinic
- Avera Cancer Institute
- Sanford USD Medical Center - Sioux Falls
- Avera Cancer Institute at Yankton
- Saint Joseph Regional Cancer Center
- Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
- Ben Taub General Hospital
- Michael E DeBakey VA Medical Center
- Huntsman Cancer Institute/University of Utah
- Norris Cotton Cancer Center-North
- Centra Lynchburg Hematology-Oncology Clinic Inc
- Virginia Cancer Institute
- Virginia Commonwealth University/Massey Cancer Center
- VCU Community Memorial Health Center
- Shenandoah Oncology PC
- Providence Regional Cancer System-Aberdeen
- FHCC Overlake
- PeaceHealth Saint Joseph Medical Center
- Harrison Medical Center
- Highline Medical Center-Main Campus
- Providence Regional Cancer System-Centralia
- Swedish Cancer Institute-Edmonds
- Saint Elizabeth Hospital
- Providence Regional Cancer Partnership
- Saint Francis Hospital
- Swedish Cancer Institute-Issaquah
- Kadlec Clinic Hematology and Oncology
- Seattle Cancer Care Alliance at EvergreenHealth
- Providence Regional Cancer System-Lacey
- Saint Clare Hospital
- PeaceHealth Saint John Medical Center
- Jefferson Healthcare
- Valley Medical Center
- Pacific Gynecology Specialists
- Swedish Medical Center-Ballard Campus
- Swedish Medical Center-Cherry Hill
- Swedish Medical Center-First Hill
- FHCC at Northwest Hospital
- PeaceHealth United General Medical Center
- Providence Regional Cancer System-Shelton
- Franciscan Research Center-Northwest Medical Plaza
- PeaceHealth Southwest Medical Center
- Providence Saint Mary Regional Cancer Center
- Providence Regional Cancer System-Yelm
- West Virginia University Charleston Division
- Duluth Clinic Ashland
- Aurora Cancer Care-Southern Lakes VLCC
- Marshfield Medical Center-EC Cancer Center
- Mayo Clinic Health System-Eau Claire Clinic
- Aurora Health Care Germantown Health Center
- Aurora Cancer Care-Grafton
- Aurora BayCare Medical Center
- Aurora Cancer Care-Kenosha South
- Gundersen Lutheran Medical Center
- Mayo Clinic Health System-Franciscan Healthcare
- University of Wisconsin Carbone Cancer Center
- Aurora Bay Area Medical Group-Marinette
- Marshfield Medical Center-Marshfield
- Aurora Cancer Care-Milwaukee
- Aurora Saint Luke's Medical Center
- Aurora Sinai Medical Center
- Marshfield Clinic-Minocqua Center
- ProHealth D N Greenwald Center
- ProHealth Oconomowoc Memorial Hospital
- Vince Lombardi Cancer Clinic - Oshkosh
- Aurora Cancer Care-Racine
- Marshfield Medical Center-Rice Lake
- Vince Lombardi Cancer Clinic-Sheboygan
- Marshfield Medical Center-River Region at Stevens Point
- Aurora Medical Center in Summit
- Vince Lombardi Cancer Clinic-Two Rivers
- ProHealth Waukesha Memorial Hospital
- UW Cancer Center at ProHealth Care
- Aurora Cancer Care-Milwaukee West
- Aurora West Allis Medical Center
- Marshfield Medical Center - Weston
- Billings Clinic-Cody
- Welch Cancer Center
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Arm I (enzalutamide, rucaparib)
Arm II (enzalutamide, placebo)
Patients receive enzalutamide PO QD and rucaparib PO BID. Patients who did not undergo bilateral orchiectomy also receive ADT consisting of leuprolide acetate IM, goserelin acetate SC every 12 weeks or degarelix SC. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients receive enzalutamide PO QD and placebo PO BID. Patients who did not undergo bilateral orchiectomy also receive ADT consisting of leuprolide acetate IM, goserelin acetate SC every 12 weeks or degarelix SC. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.