Trial Condition(s):

metastatic castrate resistant prostate cancer (mCRPC)

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

Bayer Identifier:

20510

ClinicalTrials.gov Identifier:

NCT04597125

EudraCT Number:

2019-000476-42

Recruiting

Trial Purpose

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.

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.

Trial Summary

Enrollment Goal
696
Trial Dates
black-arrow
Phase
4
Could I receive a placebo?
No
Products
Xofigo (Radium-223 dichloride, BAY88-8223)
Accepts Healthy Volunteers
No

Where to Participate

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Locations
Status
LocationsStatus
Locations

The Hospital of Lithuanian University of Health SciencesLUHS

Kaunas, Lithuania, LT-50009

Status
Recruiting
 
Locations

PI Klaipedos University Hospital

Klaipeda, Lithuania, LT-92288

Status
Recruiting
 
Locations

National Cancer Institute

Vilnius, Lithuania, LT-08660

Status
Recruiting
 
Locations

Vilnius University Hospital Santaros Klinikos

Vilnius, Lithuania, LT-08661

Status
Recruiting
 
Locations

Fakultni Nemocnice Olomouc

Olomouc, Czech Republic, 77900

Status
Not yet recruiting
 
Locations

Fakultni Thomayerova Nemocnice

Praha 4, Czech Republic, 140 59

Status
Recruiting
 
Locations

Nemocnice Chomutov, o.z.

Chomutov, Czech Republic, 430 12

Status
Recruiting
 
Locations

Fakultní nemocnice Bulovka

Praha 8, Czech Republic, 180 81

Status
Not yet recruiting
 
Locations

Fakultni nemocnice u sv. Anny

Brno, Czech Republic, 656 91

Status
Recruiting
 
Locations

Urocentrum Praha, s.r.o.

Praha 2, Czech Republic, 120 00

Status
Recruiting
 
Locations

Vseobecna fakultni nemocnice v Praze

Praha 2, Czech Republic, 128 08

Status
Recruiting
 
Locations

Krajska Nemocnice Liberec a.s.

Liberec, Czech Republic, 460 63

Status
Recruiting
 
Locations

Lady Davis Carmel Medical Center

Haifa, Israel, 3436212

Status
Recruiting
 
Locations

Tel-Aviv Sourasky Medical Center

Tel Aviv, Israel, 6423906

Status
Recruiting
 
Locations

Institut Gustave Roussy - Département de Médecine Oncologique

VILLEJUIF CEDEX, France, 94805

Status
Recruiting
 
Locations

Dokuz Eylul Universitesi Tip Fakultesi

Izmir, Turkey, 35330

Status
Recruiting
 
Locations

Koc Universitesi Tip Fakultesi - Radyoloji

Istanbul, Turkey, 34010

Status
Not yet recruiting
 
Locations

Medipol Universitesi Tip Fakultesi

Istanbul, Turkey, 34810

Status
Recruiting
 
Locations

Izmir Tepecik Egitim ve Arastirma Hastanesi

Izmir, Turkey, 35020

Status
Recruiting
 
Locations

Gaziantep Universitesi Tip Fakultesi

Gaziantep, Turkey, 27010

Status
Recruiting
 
Locations

Istanbul Universitesi Istanbul Tip Fakultesi

Istanbul, Turkey, 34093

Status
Recruiting
 
Locations

Erciyes Universitesi Tip Fakultesi

Kayseri, Turkey, 38039

Status
Recruiting
 
Locations

Hacettepe Universitesi Tip Fakultesi

Ankara, Turkey, 06100

Status
Recruiting
 
Locations

Ege Universitesi Tip Fakultesi

Izmir, Turkey, 35100

Status
Recruiting
 
Locations

Baskent Universitesi Seyhan Hastanesi

Adana, Turkey, 1250

Status
Recruiting
 
Locations

Ondokuz Mayis Uni Tip Fakultesi

Samsun, Turkey, 55139

Status
Recruiting
 
Locations

Marmara Uni. Tip Fakultesi Pendik Egitim ve Aras. Hastanesi

Istanbul, Turkey, 34899

Status
Recruiting
 
Locations

Ankara Universitesi Tip Fakultesi Hastanesi

Ankara, Turkey

Status
Recruiting
 
Locations

Ankara Yildirim Beyazit Universitesi Tip Fakültesi

ANKARA, Turkey, 6050

Status
Recruiting
 
Locations

TC Saglik Bakanligi Goztepe ProfDr Suleyman Yalcin Sehir Has

Istanbul, Turkey, 34772

Status
Recruiting
 
Locations

Trakya Univ. Tip Fak.

Edirne, Turkey, 22030

Status
Recruiting
 
Locations

Consorcio Hospitalario Provincial de Castellón

Castellón, Spain, 12002

Status
Recruiting
 
Locations

Hospital Universitari Son Espases

Palma de Mallorca, Spain, 07120

Status
Recruiting
 
Locations

Hospital Universitario 12 de Octubre

Madrid, Spain, 28041

Status
Recruiting
 
Locations

Instituto Valenciano de Oncología

Valencia, Spain, 46009

Status
Recruiting
 
Locations

Hospital Universitari Germans Trias i Pujol

Badalona (Barcelona), Spain, 08916

Status
Recruiting
 
Locations

Ciutat Sanitaria i Universitaria de la Vall d'Hebron

Barcelona, Spain, 08035

Status
Recruiting
 
Locations

Hospital Universitario Clinica Puerta de Hierro

Majadahonda, Spain, 28222

Status
Recruiting
 
Locations

Hospital de la Santa Creu i de Sant Pau

Barcelona, Spain, 08025

Status
Recruiting
 
Locations

Centro Oncológico de Galicia

A Coruña, Spain, 15009

Status
Recruiting
 
Locations

Asan Medical Center

Seoul, South Korea, 05505

Status
Recruiting
 
Locations

Seoul St. Mary's Hospital

Seoul, South Korea, 06591

Status
Recruiting
 
Locations

National Cancer Center

Goyang-si, South Korea, 10408

Status
Recruiting
 
Locations

Seoul National University Bundang Hospital

Seongnam-si, South Korea, 463-707

Status
Recruiting
 
Locations

Seoul National University Hospital

Seoul, South Korea, 03080

Status
Recruiting
 
Locations

Queen Mary Hospital

Hong Kong, Hong Kong, China

Status
Recruiting
 
Locations

Prince of Wales Hospital Hong Kong

Shatin, Hong Kong, China

Status
Recruiting
 
Locations

Pamela Youde Nethersole Eastern Hospital

Chai Wan, Hong Kong, China

Status
Recruiting
 
Locations

Tuen Mun Hospital

Hong Kong, Hong Kong, China

Status
Recruiting
 
Locations

Hong Kong Integrated Oncology Centre

Hong Kong, Hong Kong, China

Status
Not yet recruiting
 
Locations

Taipei Veterans General Hospital

Taipei, Taiwan, China, 11217

Status
Recruiting
 
Locations

Chang Gung Memorial Hospital at Linkou

Taoyuan, Taiwan, China, 33305

Status
Recruiting
 
Locations

Taichung Veterans General Hospital

Taichung, Taiwan, China, 40705

Status
Recruiting
 
Locations

National Cheng Kung University Hospital

Tainan, Taiwan, China, 704

Status
Recruiting
 
Locations

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung, Taiwan, China, 807

Status
Recruiting
 
Locations

Istanbul Universitesi Cerrahpasa-Cerrahpasa Tip Fakultesi

Istanbul, Turkey, 34098

Status
Recruiting
 
Locations

APSS Trento

Trento, Italy, 38100

Status
Recruiting
 
Locations

E.O. Ospedali Galliera

Genova, Italy, 16128

Status
Recruiting
 
Locations

A.O.U. di Modena - Policlinico

Modena, Italy, 41124

Status
Not yet recruiting
 
Locations

A.O. Santa Maria Terni

Terni, Italy, 05100

Status
Not yet recruiting
 
Locations

IRCCS Centro di Riferimento Oncologico (CRO)

Pordenone, Italy, 33081

Status
Not yet recruiting
 
Locations

Istituto Oncologico Veneto IRCCS (IOV)

Padova, Italy, 35128

Status
Recruiting
 
Locations

A.O.U. di Parma

Parma, Italy, 43126

Status
Recruiting
 
Locations

IRCCS Istituto Europeo di Oncologia s.r.l. (IEO)

Milano, Italy, 20141

Status
Recruiting
 
Locations

A.O. Nazionale SS Antonio e Biagio e Cesare Arrigo

Alessandria, Italy, 15121

Status
Recruiting
 
Locations

A.O.U. di Ferrara

Ferrara, Italy, 44124

Status
Recruiting
 
Locations

AUSL-IRCCS di Reggio Emilia

Reggio Emilia, Italy, 42123

Status
Not yet recruiting
 
Locations

A.O.R.N. Antonio Cardarelli

Napoli, Italy, 80131

Status
Not yet recruiting
 
Locations

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, Italy, 00168

Status
Recruiting
 
Locations

Beatson West of Scotland Cancer Centre

Glasgow, United Kingdom, G12 0YN

Status
Completed
 
Locations

Royal Berkshire Hospital

Reading, United Kingdom, RG1 5AN

Status
Recruiting
 
Locations

Mersin Universitesi Tip Fakultesi

Mersin, Turkey, 33070

Status
Recruiting
 
Locations

Klinik Ottakring - Wilhelminenspital

Wien, Austria, 1160

Status
Recruiting
 
Locations

Kepler Universitätsklinikum Campus III

Linz, Austria, 4020

Status
Recruiting
 
Locations

Istanbul Egitim ve Arastirma Hastanesi

Istanbul, Turkey, 34098

Status
Recruiting
 
Locations

Institut de Cancérologie de Lorraine - Alexis Vautrin

VANDOEUVRE LES NANCY, France, 54000

Status
Recruiting
 
Locations

Centre Georges Francois Leclerc Dijon

DIJON, France, 21079

Status
Recruiting
 
Locations

Centre Oscar Lambret - Lille

LILLE CEDEX, France, 59020

Status
Not yet recruiting
 
Locations

Centre de Lutte Contre le Cancer François Baclesse

CAEN CEDEX 5, France, 14076

Status
Recruiting
 
Locations

Centre Antoine Lacassagne

NICE CEDEX 2, France, 06102

Status
Recruiting
 
Locations

Centre Hospitalier Universitaire - Grenoble

GRENOBLE, France, 38043

Status
Not yet recruiting
 
Locations

Centre Eugène Marquis - Rennes Cedex

Rennes, France, 35042

Status
Recruiting
 
Locations

Hôpital Henri Mondor

CRETEIL, France, 94010

Status
Recruiting
 
Locations

Hôpital Morvan - Brest

BREST, France, 29285

Status
Recruiting
 
Locations

CHU STRASBOURG - Hôpital de Hautepierre

STRASBOURG, France, 67098

Status
Recruiting
 
Locations

Hôpital Saint André - Bordeaux

BORDEAUX, France, 33000

Status
Recruiting
 
Locations

Hôpital Bretonneau

TOURS, France, 37044

Status
Not yet recruiting
 
Locations

Szpital Wojewodzki im. Mikolaja Kopernika w Koszalinie

Koszalin, Poland, 75-851

Status
Recruiting
 
Locations

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie

Krakow, Poland, 31-115

Status
Recruiting
 
Locations

Szpital Grochowski im. dr.med. Rafala Masztaka

Warszawa, Poland, 04-073

Status
Recruiting
 
Locations

Uniwersytecki Szpital Kliniczny UM we Wroclawiu

Wroclaw, Poland, 50-556

Status
Recruiting
 
Locations

Tampereen yliopistollinen sairaala, keskussairaala

Tampere, Finland, 33520

Status
Recruiting
 
Locations

Seinäjoen keskussairaala

Seinäjoki, Finland, FIN 60220

Status
Recruiting
 
Locations

Docrates Klinikka

Helsinki, Finland, 00180

Status
Completed
 
Locations

Oulun yliopistollinen sairaala

Oulu, Finland, 90029

Status
Recruiting
 
Locations

Singapore General Hospital

Singapore, Singapore, 169608

Status
Recruiting
 
Locations

National Cancer Center Singapore

Singapore, Singapore, 169610

Status
Recruiting
 
Locations

Semmelweis University

Budapest, Hungary, 1086

Status
Not yet recruiting
 
Locations

Clinical Oncological Dispensary of Omsk Region

Omsk, Russia, 644013

Status
Not yet recruiting
 
Locations

Chelyabinsk Regional Oncology Dispensary

Chelyabinsk, Russia, 454087

Status
Recruiting
 
Locations

National Medical Research Radiology Center

Obninsk, Russia, 249036

Status
Recruiting
 
Locations

Samara Regional Clinical Oncology Dispensary

Samara, Russia, 443031

Status
Not yet recruiting
 
Locations

Tomsk National Research Medical Center of RAS

Tomsk, Russia, 634009

Status
Not yet recruiting
 
Locations

Icon Cancer Care

Brisbane, Australia, 4101

Status
Recruiting
 
Locations

Tasman Health Care

Southport, Australia, 4215

Status
Recruiting
 
Locations

Specialist Services Medical Group

Castle Hill, Australia, 2154

Status
Recruiting
 
Locations

Nepean Hospital

Penrith, Australia, 2757

Status
Recruiting
 
Locations

Prince of Wales Hospital NSW

Randwick, Australia, 2031

Status
Recruiting
 
Locations

North West Cancer Centre

North Tamworth, Australia, 2340

Status
Recruiting
 
Locations

Royal Adelaide Hospital

Adelaide, Australia, 5000

Status
Recruiting
 
Locations

Wollongong Private Hospital

Wollongong, Australia, 2500

Status
Recruiting
 
Locations

The Tweed Hospital

Tugun, Australia, 4224

Status
Recruiting
 
Locations

Universitätsklinikum Münster (UKM)

Münster, Germany, 48149

Status
Recruiting
 
Locations

Universitätsmedizin der Johannes Gutenberg Universität Mainz

Mainz, Germany, 55131

Status
Recruiting
 
Locations

Institut de Cancérologie Jean Godinot

REIMS cedex, France, 51726

Status
Recruiting
 
Locations

Hospital Virgen de la Victoria

Málaga, Spain, 29010

Status
Recruiting
 
Locations

Institut Claudius Regaud - iUCT Oncopole

TOULOUSE CEDEX 9, France, 31059

Status
Not yet recruiting
 
Locations

Institut Paoli-Calmettes - Marseille

MARSEILLE, France, 13273

Status
Recruiting
 
Locations

Northern Cancer Institute

St Leonards, Australia, 2065

Status
Recruiting
 
Locations

The Wesley Hospital

Auchenflower, Australia, 4066

Status
Not yet recruiting
 
Locations

Izmir Ekonomi Universitesi Medikal Point Hastanesi

Izmir, Turkey, 35575

Status
Recruiting
 
Locations

Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz

Szolnok, Hungary, H-5004

Status
Not yet recruiting
 
Locations

Scanmed SA ZOZ Gastromed

Lublin, Poland, 20-582

Status
Recruiting
 
Locations

Hospital Lucus Augustí

Lugo, Spain, 27003

Status
Not yet recruiting
 
Locations

Complejo Hospitalario de Jaén

Jaén, Spain, 23007

Status
Not yet recruiting
 
Locations

Hospital Clínico Universitario de Santiago de Compostela

Santiago de Compostela, Spain, 15706

Status
Not yet recruiting
 
Locations

Hospital Universitario Puerta del Mar

Cádiz, Spain, 11009

Status
Not yet recruiting
 
Locations

Swietokrzyskie Centrum Onkologii

Kielce, Poland, 25-734

Status
Not yet recruiting
 
Locations

Hospital Central de Asturias

Oviedo, Spain, 33011

Status
Recruiting
 
Locations

Royal Free Hospital

London, United Kingdom, NW3 2QG

Status
Not yet recruiting
 
Locations

I.C.O Girona

Girona, Spain, 17007

Status
Recruiting
 
Locations

Universitätsmedizin Göttingen

Göttingen, Germany, D-37077

Status
Not yet recruiting
 
Locations

Gosford Hospital (GH) - Central Coast Cancer Centre

Gosford, Australia, 2250

Status
Not yet recruiting
 
Locations

Wollongong Hospital

Wollongong, Australia, 2521

Status
Not yet recruiting
 

Trial Design