Investigation of Radium-223 Dichloride (Xofigo), a Treatment That Gives Off Radiation That Helps Kill Cancer Cells, Compared to a Treatment That Inactivates Hormones (New Antihormonal Therapy, NAH) in Patients With Prostate Cancer That Has Spread to the Bone Getting Worse on or After Earlier NAH

A Phase 4, Randomized, Open-label, Multicenter Efficacy and Safety Study of Standard Dose of Radium-223 Dichloride vs. Standard Doses of Novel Anti-hormonal Therapy (NAH) in Patients With Bone Dominant Metastatic Castration Resistant Prostate Cancer (mCRPC) Progressing on/After One Line of NAH

Researchers in this study want to compare how well drug radium-223 dichloride (Xofigo) and new (novel) anti-hormonal (NAH) therapy work in participants with prostate gland cancer which has spread to the bone and progressed on or after one line of NAH therapy. Meanwhile researchers want to compare the safety of radium-223 dichloride and NAH therapy. Radium-223 dichloride is known as a radioactive drug that is taken up by bones after it is injected into the body. It works by giving off a type of radioactivity that travels a very short distance and kills the tumor cells that have spread to the bone without major effects to the healthy cells. It has been approved in many countries for the treatment of patients with prostate cancer which has spread to the bone. The NAH drugs used in this study will be either abiraterone acetate (Zytiga) (plus prednisone/prednisolone) or enzalutamide (Xtandi). Both of them are standard approved medications which are used in the treatment of advanced prostate cancer.

Participants in this study will receive either Radium-223 dichloride or a NAH therapy. Radium-223 dichloride will be given as an infusion into one of the veins on Day 1 of each 4-week cycle for a total of up to 6 cycles. Oral NAH therapy will be given per the standard approved dose once daily until the disease has progressed. Participants will visit the hospital or clinic every 2 weeks for the first 6 cycles, and only on the first day of each cycle from cycle 7 and onwards. Observation for each participant will last for about 2 years in total. Blood and urine samples will be collected from the participants and participants will be asked to complete questionnaires about the well-being and the pain.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Castrate Resistant Prostate Cancer (mCRPC)
• Intervention / Treatment: Drug: Radium-223 dichloride (Xofigo, BAY88-8223); Drug: NAH therapy

• Study Type: Interventional
• Enrollment (Estimated): 696
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Bayer Clinical Trials Contact; Phone Number: (+)1-888-84 22937; Email: clinical-trials-contact@bayer.com

Study Locations

• Australia
  • Penrith, Australia, 2757
    • Recruiting
    • Nepean Hospital
  • New South Wales
    • Castle Hill, New South Wales, Australia, 2154
      • Recruiting
      • Specialist Services Medical Group
    • Gosford, New South Wales, Australia, 2250
      • Recruiting
      • Gosford Hospital
    • North Tamworth, New South Wales, Australia, 2340
      • Recruiting
      • North West Cancer Centre
    • Randwick, New South Wales, Australia, 2031
      • Recruiting
      • Prince of Wales Hospital NSW
    • St Leonards, New South Wales, Australia, 2065
      • Recruiting
      • Northern Cancer Institute
    • Wollongong, New South Wales, Australia, 2500
      • Recruiting
      • Illawarra Shoalhaven Local Health District
    • Wollongong, New South Wales, Australia, 2521
      • Withdrawn
      • Illawarra Shoalhaven Local Health District
  • Queensland
    • Auchenflower, Queensland, Australia, 4066
      • Withdrawn
      • The Wesley Hospital
    • Brisbane, Queensland, Australia, 4101
      • Recruiting
      • ICON Cancer Care
    • Southport, Queensland, Australia, 4215
      • Recruiting
      • Tasman Health Care
    • Tugun, Queensland, Australia, 4224
      • Recruiting
      • The Tweed Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Recruiting
      • Royal Adelaide Hospital
    • North Adelaide, South Australia, Australia, 5006
      • Withdrawn
      • Calvary North Adelaide Hospital
• Austria
  • Wien, Austria, 1160
    • Recruiting
    • Klinik Ottakring - Wilhelminenspital
  • Oberösterreich
    • Linz, Oberösterreich, Austria, 4020
      • Recruiting
      • Kepler Universitätsklinikum Campus III
• Czechia
  • Brno, Czechia, 656 91
    • Recruiting
    • Fakultni nemocnice u sv. Anny
  • Chomutov, Czechia, 430 12
    • Recruiting
    • Nemocnice Chomutov, o.z.
  • Liberec, Czechia, 460 63
    • Recruiting
    • Krajská nemocnice Liberec
  • Olomouc, Czechia, 77900
    • Not yet recruiting
    • Fakultní nemocnice Olomouc
  • Prague, Czechia, 140 59
    • Recruiting
    • Fakultni Thomayerova nemocnice
  • Praha 2, Czechia, 12808
    • Recruiting
    • Vseobecna fakultni nemocnice v Praze
  • Praha 2, Czechia, 120 00
    • Recruiting
    • Urocentrum Praha, s.r.o.
  • Praha 8, Czechia, 180 81
    • Recruiting
    • Fakultni nemocnice Bulovka
• Finland
  • Helsinki, Finland, 00180
    • Completed
    • Docrates Klinikka
  • Kuopio, Finland, 70210
    • Withdrawn
    • Kuopion Yliopistollinen Sairaala
  • Oulu, Finland, 90029
    • Recruiting
    • Oulun yliopistollinen sairaala
  • Seinäjoki, Finland, FIN 60220
    • Recruiting
    • Seinäjoen keskussairaala
  • Tampere, Finland, 33520
    • Recruiting
    • Tampereen yliopistollinen sairaala, keskussairaala
• France
  • Besancon, France, 25030
    • Withdrawn
    • Hôpital Jean Minjoz
  • Bordeaux, France, 33000
    • Recruiting
    • Hôpital Saint André - Bordeaux
  • Bordeaux, France, 33076
    • Withdrawn
    • Institut Bergonié - Unicancer Nouvelle Aquitaine
  • Brest, France, 29285
    • Recruiting
    • Hôpital Morvan - Brest
  • Caen Cedex 5, France, 14076
    • Recruiting
    • Centre de Lutte Contre le Cancer François Baclesse
  • Creteil, France, 94010
    • Recruiting
    • Hopital Henri Mondor
  • Dijon, France, 21079
    • Recruiting
    • Centre Georges Francois Leclerc Dijon
  • Grenoble, France, 38700
    • Recruiting
    • Centre Hospitalier Universitaire - Grenoble
  • Hyeres, France, 83400
    • Withdrawn
    • Clinique Sainte Marguerite - Hyères
  • Lille Cedex, France, 59020
    • Withdrawn
    • Centre Oscar Lambret - Lille
  • Lyon, France, 69008
    • Withdrawn
    • Centre Leon Berard
  • Marseille, France, 13273
    • Recruiting
    • Institut Paoli-Calmettes - Marseille
  • Montpellier Cedex, France, 34298
    • Withdrawn
    • Institut du Cancer de Montpellier - Val d'Aurelle
  • Nice Cedex 2, France, 06102
    • Recruiting
    • Centre Antoine Lacassagne
  • Reims, France, 51726
    • Recruiting
    • Institut de Cancérologie Jean Godinot
  • Rennes, France, 35042
    • Recruiting
    • Centre Eugène Marquis - Rennes Cedex
  • Strasbourg, France, 67098
    • Recruiting
    • CHU STRASBOURG - Hôpital de Hautepierre
  • Toulouse Cedex 9, France, 31059
    • Withdrawn
    • Institut Claudius Régaud - IUCT Oncopole
  • Tours, France, 37044
    • Not yet recruiting
    • Hôpital Bretonneau
  • Vandoeuvre-les-Nancy, France, 54519
    • Recruiting
    • Institut de Cancérologie de Lorraine - Alexis Vautrin
  • Villejuif Cedex, France, 94805
    • Recruiting
    • Institut Gustave Roussy - Département de Médecine Oncologique
• Germany
  • Bremen, Germany, 28277
    • Withdrawn
    • Urologische Gemeinschaftspraxis Bremen
  • Göttingen, Germany, D-37077
    • Withdrawn
    • Universitätsmedizin Göttingen - Hämatologie und medizin. Onkologie
  • Nordrhein-Westfalen
    • Münster, Nordrhein-Westfalen, Germany, 48149
      • Recruiting
      • Universitätsklinikum Münster (UKM)
  • Rheinland-Pfalz
    • Mainz, Rheinland-Pfalz, Germany, 55131
      • Recruiting
      • Universitätsmedizin der Johannes Gutenberg Universität Mainz
  • Sachsen
    • Dresden, Sachsen, Germany, 01307
      • Withdrawn
      • Universitatsklinikum Carl Gustav Carus Dresden
• Hong Kong
  • Central, Hong Kong
    • Not yet recruiting
    • Hong Kong Integrated Oncology Centre (HKIOC)
  • Chai Wan, Hong Kong
    • Recruiting
    • Pamela Youde Nethersole Eastern Hospital
  • Hong Kong, Hong Kong
    • Recruiting
    • Queen Mary Hospital
  • Hong Kong, Hong Kong
    • Recruiting
    • Tuen Mun Hospital
  • Hong Kong, Hong Kong
    • Withdrawn
    • Hong Kong Sanatorium & Hospital
  • Shatin, Hong Kong, MISSING
    • Recruiting
    • Prince of Wales Hospital
• Hungary
  • Budapest, Hungary, 1062
    • Withdrawn
    • Magyar Honvedseg Egeszsegugyi Kozpont
  • Budapest, Hungary, 1086
    • Recruiting
    • Semmelweis University
  • Debrecen, Hungary, 4032
    • Withdrawn
    • Debreceni Egyetem Klinikai Kozpont
  • Szekszard, Hungary, 7100
    • Withdrawn
    • Tolna Varmegyei Balassa Janos Korhaz
  • Szolnok, Hungary, H-5004
    • Recruiting
    • Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz
• Israel
  • Haifa, Israel, 3436212
    • Recruiting
    • Lady Davis Carmel Medical Center
  • Haifa, Israel, 3109601
    • Withdrawn
    • Rambam Health Corporation
  • Holon, Israel, 5822012
    • Withdrawn
    • Edith Wolfson Medical Center
  • Jerusalem, Israel, 9112001
    • Withdrawn
    • Hadassah Hebrew University Hospital Ein Kerem
  • Petah Tikva, Israel, 4941492
    • Withdrawn
    • Clalit Health Services Rabin Medical Center-Beilinson Campus
  • Tel Aviv, Israel, 6423906
    • Recruiting
    • Tel-Aviv Sourasky Medical Center
• Italy
  • Campania
    • Napoli, Campania, Italy, 80131
      • Not yet recruiting
      • A.O.R.N. Antonio Cardarelli
  • Emilia-Romagna
    • Ferrara, Emilia-Romagna, Italy, 44124
      • Recruiting
      • A.O.U. di Ferrara
    • Modena, Emilia-Romagna, Italy, 41124
      • Recruiting
      • A.O.U. di Modena - Policlinico
    • Parma, Emilia-Romagna, Italy, 43126
      • Recruiting
      • A.O.U. di Parma
    • Reggio Emilia, Emilia-Romagna, Italy, 42123
      • Not yet recruiting
      • AUSL-IRCCS di Reggio Emilia
  • Friuli-Venezia Giulia
    • Pordenone, Friuli-Venezia Giulia, Italy, 33081
      • Recruiting
      • Irccs Centro Di Riferimento Oncologico (CRO)
  • Lazio
    • Roma, Lazio, Italy, 00168
      • Recruiting
      • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
  • Liguria
    • Genova, Liguria, Italy, 16128
      • Recruiting
      • E.O. Ospedali Galliera
  • Lombardia
    • Milano, Lombardia, Italy, 20141
      • Recruiting
      • IRCCS Istituto Europeo di Oncologia s.r.l. (IEO)
  • Piemonte
    • Alessandria, Piemonte, Italy, 15121
      • Recruiting
      • A.O. Nazionale SS Antonio e Biagio e Cesare Arrigo - Oncologia
  • Toscana
    • Pisa, Toscana, Italy, 56126
      • Withdrawn
      • A.O.U. Pisana
  • Trentino-Alto Adige
    • Trento, Trentino-Alto Adige, Italy, 38100
      • Recruiting
      • APSS Trento
  • Umbria
    • Terni, Umbria, Italy, 05100
      • Withdrawn
      • A.O. Santa Maria Terni
  • Veneto
    • Padova, Veneto, Italy, 35128
      • Recruiting
      • Istituto Oncologico Veneto IRCCS (IOV)
• Korea, Republic of
  • Seoul, Korea, Republic of, 06591
    • Recruiting
    • Seoul st. mary's hospital
  • Seoul, Korea, Republic of, 138-736
    • Recruiting
    • Asan Medical Center
  • Gyeonggido
    • Goyang-si, Gyeonggido, Korea, Republic of, 10408
      • Recruiting
      • National Cancer Center
    • Seongnam-si, Gyeonggido, Korea, Republic of, 463-707
      • Recruiting
      • Seoul National University Bundang Hospital
  • Seoul Teugbyeolsi
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 3080
      • Terminated
      • Seoul National University Hospital
• Lithuania
  • Kaunas, Lithuania, LT-50009
    • Recruiting
    • The Hospital of Lithuanian University of Health SciencesLUHS
  • Klaipeda, Lithuania, LT-92288
    • Recruiting
    • PI Klaipedos University Hospital
  • Vilnius, Lithuania, LT-08660
    • Recruiting
    • National Cancer Institute
  • Vilnius, Lithuania, LT-08661
    • Completed
    • Vilnius University hospital Santaros klinikos
• Poland
  • Bydgoszcz, Poland, 85-796
    • Withdrawn
    • Centrum Onkologii im. Prof. Franciszka Lukaszczyka
  • Kielce, Poland, 25-734
    • Withdrawn
    • Swietokrzyskie Centrum Onkologii
  • Koszalin, Poland, 75-851
    • Recruiting
    • Szpital Wojewodzki im. Mikolaja Kopernika w Koszalinie - Oddzial Dzienny Chemioterapii
  • Krakow, Poland, 31-115
    • Recruiting
    • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie
  • Lublin, Poland, 20-582
    • Recruiting
    • Scanmed SA ZOZ Gastromed
  • Warszawa, Poland, 04-073
    • Recruiting
    • Szpital Grochowski im. dr.med. Rafala Masztaka
  • Wroclaw, Poland, 50-556
    • Completed
    • Uniwersytecki Szpital Kliniczny UM we Wroclawiu
• Russian Federation
  • Chelyabinsk, Russian Federation, 454087
    • Completed
    • Chelyabinsk Regional Oncology Dispensary
  • Moscow, Russian Federation, 115552
    • Withdrawn
    • Russian Oncological Scientific Center n.a. N.N. Blokhin RAMS
  • Obninsk, Russian Federation, 249036
    • Completed
    • National Medical Research Radiology Center
  • Omsk, Russian Federation, 644013
    • Withdrawn
    • Clinical Oncological Dispensary of Omsk Region
  • Samara, Russian Federation, 443031
    • Withdrawn
    • Samara Regional Clinical Oncology Dispensary
  • Tomsk, Russian Federation, 634009
    • Withdrawn
    • Tomsk National Research Medical Center of RAS
• Singapore
  • Singapore, Singapore, 169610
    • Recruiting
    • National Cancer Center Singapore
  • Singapore, Singapore, 169608
    • Recruiting
    • Singapore General Hospital
• Spain
  • A Coruña, Spain, 15009
    • Recruiting
    • Centro Oncológico de Galicia
  • Barcelona, Spain, 08035
    • Recruiting
    • Ciutat Sanitaria i Universitaria de la Vall d'Hebron
  • Barcelona, Spain, 08025
    • Recruiting
    • Hospital de la Santa Creu i Sant Pau | Gynecology Department
  • Castellón, Spain, 12002
    • Recruiting
    • Consorcio Hospitalario Provincial de Castellón
  • Girona, Spain, 17007
    • Recruiting
    • I.C.O Girona
  • Jaén, Spain, 23007
    • Recruiting
    • Complejo Hospitalario de Jaen
  • Lugo, Spain, 27003
    • Recruiting
    • Hospital Lucus Augusti
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario 12 de octubre
  • Madrid, Spain, 28034
    • Withdrawn
    • Hospital Universitario Ramon y Cajal | Departamento de Medicina Interna
  • Málaga, Spain, 29010
    • Recruiting
    • Hospital Universitario Virgen de la Victoria | Cardiology Department
  • Valencia, Spain, 46009
    • Recruiting
    • Instituto Valenciano de Oncologia
  • A Coruña
    • Santiago de Compostela, A Coruña, Spain, 15706
      • Recruiting
      • Hospital Clinico Universitario de Santiago de Compostela
  • Andalucía
    • Cadiz, Andalucía, Spain, 11009
      • Recruiting
      • Hospital Universitario Puerta Del Mar
  • Asturias
    • Oviedo, Asturias, Spain, 33011
      • Recruiting
      • Hospital Central de Asturias
  • Barcelona
    • Badalona (Barcelona), Barcelona, Spain, 08916
      • Recruiting
      • Hospital Universitari Germans Trias i Pujol
  • Illes Baleares
    • Palma de Mallorca, Illes Baleares, Spain, 07120
      • Recruiting
      • Hospital Universitari Son Espases
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Recruiting
      • Hospital Universitario Clinica Puerta de Hierro
• Taiwan
  • Taichung, Taiwan, 40705
    • Recruiting
    • Taichung Veterans General Hospital
  • Tainan, Taiwan, 704
    • Recruiting
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 11217
    • Completed
    • Taipei Veterans General Hospital
  • Taoyuan, Taiwan, 33305
    • Recruiting
    • Chang Gung Memorial Hospital at Linkou
  • Kaohsiung
    • Kaohsiung City, Kaohsiung, Taiwan, 807377
      • Recruiting
      • Kaohsiung Medical University Chung-Ho Memorial Hospital
• Turkey
  • Adana, Turkey, 1250
    • Recruiting
    • Baskent Universitesi Seyhan Hastanesi
  • Ankara, Turkey, 06100
    • Recruiting
    • Hacettepe Universitesi Tip Fakultesi
  • Ankara, Turkey
    • Recruiting
    • Ankara Universitesi Tip Fakultesi Hastanesi
  • Ankara, Turkey, 6050
    • Recruiting
    • Ankara Yildirim Beyazit Universitesi Tip Fakültesi
  • Edirne, Turkey, 22030
    • Recruiting
    • Trakya Univ. Tip Fak.
  • Gaziantep, Turkey, 27010
    • Recruiting
    • Gaziantep Universitesi Tip Fakultesi
  • Istanbul, Turkey, 34093
    • Recruiting
    • Istanbul Universitesi Istanbul Tip Fakultesi
  • Istanbul, Turkey, 34098
    • Recruiting
    • Istanbul Universitesi Cerrahpasa-Cerrahpasa Tip Fakultesi
  • Istanbul, Turkey, 34098
    • Recruiting
    • Istanbul Egitim ve Arastirma Hastanesi
  • Istanbul, Turkey, 34772
    • Recruiting
    • TC Saglik Bakanligi Goztepe ProfDr Suleyman Yalcin Sehir Has
  • Istanbul, Turkey, 34810
    • Recruiting
    • Medipol Universitesi Tip Fakultesi
  • Istanbul, Turkey, 34899
    • Recruiting
    • Marmara Uni. Tip Fakultesi Pendik Egitim ve Aras. Hastanesi
  • Istanbul, Turkey, 34010
    • Withdrawn
    • Koc Universitesi Tip Fakultesi - Radyoloji
  • Izmir, Turkey, 35100
    • Recruiting
    • Ege Universitesi Tip Fakultesi
  • Izmir, Turkey, 35330
    • Recruiting
    • Dokuz Eylul Universitesi Tip Fakultesi
  • Izmir, Turkey, 35020
    • Recruiting
    • Izmir Tepecik Egitim ve Arastirma Hastanesi
  • Karsiyaka, Turkey, 35575
    • Recruiting
    • Izmir Ekonomi Universitesi Medikal Point Hastanesi
  • Kayseri, Turkey, 38039
    • Recruiting
    • Erciyes Universitesi Tip Fakultesi
  • Mersin, Turkey, 33070
    • Recruiting
    • Mersin Üniversitesi Tip Fakültesi
  • Samsun, Turkey, 55139
    • Recruiting
    • Ondokuz Mayis Uni Tip Fakultesi
• United Kingdom
  • Glasgow, United Kingdom, G12 0YN
    • Completed
    • Beatson West of Scotland Cancer Centre
  • London, United Kingdom, NW3 2QG
    • Withdrawn
    • Royal Free Hospital
  • Berkshire
    • Reading, Berkshire, United Kingdom, RG1 5AN
      • Recruiting
      • Royal Berkshire Hospital
  • Lancashire
    • Preston, Lancashire, United Kingdom, PR2 4HT
      • Withdrawn
      • Royal Preston Hospital
  • Surrey
    • Guildford, Surrey, United Kingdom, GU2 7XX
      • Withdrawn
      • Royal Surrey County Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants who have histologically confirmed adenocarcinoma of the prostate.
• Participants with mCRPC progressing on/after one line of an approved NAH (eg. abiraterone, enzalutamide, apalutamide, or darolutamide, after being treated for at least 3 months) in an authorized prostate cancer indication.
• One prior taxane treatment regimen (at least 2 cycles) for metastatic prostate cancer (mHSPC and mCRPC) or refusal or ineligibility of such a regimen.
• Prostate cancer progression documented by PSA according to the Prostate Cancer Working Group 3 (PCWG3) criteria or radiological progression according to RECIST, version 1.1.
• At least 2 bone metastases on bone scan within 4 weeks prior to randomization with no current or history of lung, liver, other visceral, and / or brain metastasis.
• Symptomatic prostate cancer. A worst pain score (WPS) of at least 1 on the Brief Pain Inventory-Short Form (BPI-SF) Question #3 (worst pain in last 24 hours). This is to be assessed once during the Screening period.
• Maintenance of medical castration or surgical castration with testosterone less than 50 ng/dL (1.7 nmol/L). If the participant is being treated with luteinizing hormone releasing hormone (LHRH) agonists or antagonists (participant who has not undergone orchiectomy), this therapy must have been initiated at least 4 weeks prior to randomization and must be continued throughout the study.
• Participants must be on a BHA treatment, such as bisphosphonates or denosumab treatment unless such treatment is contraindicated or not recommended per investigator's judgement and inclusion is agreed to by the medical monitor.
• Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1.
• Life expectancy ≥ 6 months.
• Able to swallow abiraterone and prednisone/prednisolone or enzalutamide as whole tablets/capsules.

• Laboratory requirements:

  • Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
  • Platelet count ≥ 100 x 10^9/L
  • Hemoglobin (Hb) ≥ 9.0 g/dL (90 g/L; 5.6 mmol/L)
  • Total bilirubin level ≤ 1.5 x institutional upper limit of normal (ULN) (except for participants with documented Gilbert's disease)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
  • Creatinine ≤ 1.5 x ULN or estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m^2 as calculated using the Cockcroft-Gault equation
  • International normalized ratio (INR) of prothrombin time (PT; PT-INR) and partial thromboplastin time (PTT) ≤ 1.5 times the ULN. Participants treated with warfarin or heparin will be allowed to participate in the study if no underlying abnormality in coagulation parameters exists per prior history; weekly evaluation of PT-INR / PTT will be required until stability is achieved (as defined by local standard of care and based on pre-study PT-INR / PTT values)
  • Serum albumin > 30 g/L
  • Serum potassium ≥ 3.5 mmol/L
• Capable of giving signed informed consent

Exclusion Criteria:

• Active infection or other medical condition that would make prednisone / prednisolone (corticosteroid) use contraindicated.
• Any chronic medical condition requiring a higher dose of corticosteroid than 10 mg prednisone / prednisolone equivalent daily for more than 2 months.
• Pathological finding consistent with tumors with predominant neuroendocrine features or small cell carcinoma of the prostate.
• History of osteoporotic fracture
• History of visceral metastasis, or presence of visceral metastasis detected by screening imaging examinations.
• History of or known brain metastasis.
• Malignant lymphadenopathy exceeding 3 cm in short-axis diameter.
• Other malignancy treated within the last 3 years (except non-melanoma skin cancer or low-grade superficial bladder cancer)
• Imminent spinal cord compression based on clinical findings and / or magnetic resonance imaging (MRI). Participants with history of spinal cord compression should have completely recovered.
• Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 95 mmHg). Participants with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment.
• Active or symptomatic viral hepatitis
• History of pituitary or adrenal dysfunction

• Any other serious illness or medical condition such as, but not limited to:

  • Any infection ≥ National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 Grade 2
  • Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class II to IV heart disease or cardiac ejection fraction measurement of <50% at baseline
  • Current clinical evidence of any uncontrolled cardiac arrhythmia
  • Crohn's disease or ulcerative colitis
  • Bone marrow dysplasia
  • Moderate and severe hepatic impairment (Child-Pugh Classes B and C)
  • Unmanageable fecal incontinence.
• Any condition, which in the opinion of the investigator would preclude participation in this trial (eg, history of seizure).
• Hypersensitivity to the active substances or to any excipients of radium-223 dichloride, or abiraterone acetate or enzalutamide.
• Prior therapeutic systemic radiation with any radiopharmaceutical medication for the treatment of prostate cancer, including but not limited to lutetium-177, strontium-89, samarium-153, iodine-131, rhenium-186, rhenium-188, or radium-223. Radiopharmaceutical compounds used for diagnosis purposes only are allowed.
• Prior hemibody external radiotherapy is excluded. Participants who received other types of prior external radiotherapy are allowed provided that the bone marrow function is assessed and meets the protocol requirements for Hb, ANC, and platelet count.
• Blood transfusion or erythropoietin stimulating agents 4 weeks prior to Screening and during the whole Screening period before randomization.
• Excessive intake of biotin above the recommended daily dose of 30 μg. Biotin is found in multivitamins, including prenatal multivitamins, biotin supplements, and dietary supplements for hair, skin, and nail growth at levels that may interfere with laboratory tests.
• Prior administration of an investigational therapeutic for CRPC.
• Previous (within the last 4 weeks of randomization) or concurrent participation in any interventional clinical study with investigational study drug administration.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; Participants with bone dominant metastatic castration resistant prostate cancer (mCRPC) progressing on/after one line of NAH will be randomized to receive radium-223 dichloride	Drug: Radium-223 dichloride (Xofigo, BAY88-8223); Participants will receive Radium-223 (BAY88-8223) every 4 weeks for a total of 6 administrations via intravenous (IV) injection
Active Comparator: Arm B; Participants with bone dominant metastatic castration resistant prostate cancer (mCRPC) progressing on/after one line of NAH will be randomized to receive second novel anti-hormonal therapy (NAH)	Drug: NAH therapy; Participants will receive continuous NAH (either Abiraterone acetate plus prednisone/prednisolone [AAP] or enzalutamide) by mouth (per os) daily; Other Names: Second novel anti-hormonal therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall survival (OS)	Up to five years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to first symptomatic skeletal event (SSE)		Up to five years
Radiological Progression-free survival (rPFS)	rPFS is defined as the time from the date of randomization to the date of confirmed radiological progression or death, whichever occurs first.	Up to five years
Time to pain progression (BPI-SF)	The Brief Pain Inventory-Short Form (BPI-SF) is a self-administered questionnaire with 11 items designed to evaluate the intensity of, and the impairment caused by pain. Four items measure pain intensity using 0 ("no pain") to 10 ("pain as bad as you can imagine") numeric rating scales, and 7 items measure the level of interference with function caused by pain using 0 (no interference) to 10 (complete interference) rating scales.	Up to five years
Adverse events assessments using NCI CTCAE (v5.0)		After first administration of study intervention up to 30 days after the last dose of study intervention
Incidence of fractures		Up to five years
Time to deterioration of FACT-P total score	The FACT-P questionnaire assesses prostate cancer-related quality of life. The FACT-P total score is the sum of the scores of 39 items of the questionnaire and ranges from 1 to 156, the higher the score, the better the quality of life of prostate cancer patients.	Up to five years

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

Helpful Links

• Click here to find information for studies related to Bayer products. To find this study enter the ClinicalTrials.gov identifier (NCT) number or Bayer Study Identifier (ID) in the search field.

Study record dates

Study Major Dates

• Study Start (Actual): November 9, 2020
• Primary Completion (Estimated): May 1, 2025
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: October 16, 2020
• First Submitted That Met QC Criteria: October 16, 2020
• First Posted (Actual): October 22, 2020

Study Record Updates

• Last Update Posted (Actual): March 28, 2024
• Last Update Submitted That Met QC Criteria: March 27, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Antineoplastic Agents; Radium Ra 223 dichloride
• Other Study ID Numbers: 20510 (City of Hope Medical Center); 2019-000476-42 (EudraCT Number); 2023-505830-89-00 (Other Identifier: CTIS (EU))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No