RADIANT: A Study of Radium-223 Dichloride (Xofigo) vs Enzalutamide or Abiraterone (ARPIs, Androgen Receptor Pathway Inhibitors) in Patients With Prostate Cancer That Has Spread to the Bones (mCRPC, Metastatic Castration-Resistant Prostate Cancer)

NCT04597125 | Active Not Recruiting Phase 4 DMC

• 3 other identifiers: 205102023-505830-89-002019-000476-42
• Study Type: interventional
• Target: 654
• Locations: 18 countries
• Sites: 107

Brief Summary

Researchers in this study want to compare how well drug radium-223 dichloride (Xofigo) and androgen receptor pathway inhibitor (ARPI) therapy work in participants with prostate gland cancer which has spread to the bone and progressed on or after one line of ARPI therapy. Meanwhile researchers want to compare the safety of radium-223 dichloride and ARPI 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 ARPI 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 ARPI 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 ARPI 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.

Conditions

Metastatic Castrate Resistant Prostate Cancer (mCRPC)

Outcome Measures

Primary Outcomes (1)

• Overall survival (OS)

  Up to five years

Secondary Outcomes (6)

• Time to first symptomatic skeletal event (SSE)

  Up to five years

• Radiological Progression-free survival (rPFS)

  Up to five years

• Time to pain progression (BPI-SF)

  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

Study Arms (2)

Arm A

EXPERIMENTAL

Participants with bone dominant metastatic castration resistant prostate cancer (mCRPC) progressing on/after one line of ARPI will be randomized to receive radium-223 dichloride

Drug: Radium-223 dichloride (Xofigo, BAY88-8223)

Arm B

ACTIVE COMPARATOR

Participants with bone dominant metastatic castration resistant prostate cancer (mCRPC) progressing on/after one line of ARPI will be randomized to receive second ARPI

Drug: ARPI therapy

Interventions

ARPI therapy DRUG

Participants will receive continuous ARPI (either Abiraterone acetate plus prednisone/prednisolone \[AAP\] or enzalutamide) by mouth (per os) daily

Also known as: Second ARPI

Arm B

Radium-223 dichloride (Xofigo, BAY88-8223) DRUG

Participants will receive Radium-223 (BAY88-8223) every 4 weeks for a total of 6 administrations via intravenous (IV) injection

Arm A

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants who have histologically confirmed adenocarcinoma of the prostate.
• Participants with mCRPC progressing on/after one line of an approved ARPI (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.
• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Bayer: lead

Study Sites (118)

Specialist Services Medical Group

Castle Hill, New South Wales, 2154, Australia

Location

Gosford Hospital

Gosford, New South Wales, 2250, Australia

Location

Nepean Hospital

Kingswood, New South Wales, 2747, Australia

Location

North West Cancer Centre

North Tamworth, New South Wales, 2340, Australia

Location

Northern Cancer Institute

St Leonards, New South Wales, 2065, Australia

Location

Prince of Wales Hospital NSW

Sydney, New South Wales, 2031, Australia

Location

Illawarra Shoalhaven Local Health District

Wollongong, New South Wales, 2500, Australia

Location

Icon Cancer Care

Brisbane, Queensland, 4101, Australia

Location

Tasman Health Care

Southport, Queensland, 4215, Australia

Location

The Tweed Hospital

Tugun, Queensland, 4224, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Klinik Ottakring - Wilhelminenspital

Vienna, Lower Austria, 3500, Austria

Location

Kepler Universitätsklinikum Campus III

Linz, Upper Austria, 4020, Austria

Location

Fakultní nemocnice u sv. Anny v Brne

Brno, 656 91, Czechia

Location

Krajska Zdravotní, a.s. - Nemocnice Chomutov, o.z. - Onkologické oddelení

Chomutov, 430 12, Czechia

Location

Krajská nemocnice Liberec, a. s.

Liberec, 460 63, Czechia

Location

Urocentrum Praha, s.r.o.

Prague, 120 00, Czechia

Location

Všeobecná fakultní nemocnice v Praze

Prague, 12808, Czechia

Location

Fakultni Thomayerova Nemocnice

Prague, 140 59, Czechia

Location

Fakultní nemocnice Bulovka

Prague, 180 81, Czechia

Location

Oulu University Hospital, Oulun yliopistollinen sairaala (OYS)

Oulu, North Ostrobothnia, 90220, Finland

Location

Tampere University Hospital, Tampereen yliopistollinen sairaala (TAYS)

Tampere, Pirkanmaa, 33520, Finland

Location

Seinäjoen keskussairaala

Seinäjoki, South Ostrobothnia, 60220, Finland

Location

OBSOLETE_Docrates Klinikka

Helsinki, Uusimaa, 00180, Finland

Location

Centre Hospitalier Universitaire - Grenoble

La Tronche (Grenoble Area), Auvergne-Rhône-Alpes, 38700, France

Location

Centre Georges Francois Leclerc Dijon

Dijon, Bourgogne-Franche-Comté, 21079, France

Location

Hôpital Morvan - Brest

Brest, Brittany Region, 29470, France

Location

Centre Eugène Marquis - Rennes Cedex

Rennes, Brittany Region, 35062, France

Location

Institut de Cancerologie Jean Godinot

Reims, Grand Est, 51726, France

Location

CHU Strasbourg - Hopital Hautepierre

Strasbourg, Grand Est, 67200, France

Location

Institut de Cancérologie de Lorraine - Alexis Vautrin

Vandœuvre-lès-Nancy, Grand Est, 54519, France

Location

Hôpital Saint André - Bordeaux

Bordeaux, New Aquitaine, 33000, France

Location

Centre de Lutte Contre le Cancer François Baclesse

Caen, Normandy, 14076, France

Location

Institut Paoli-Calmettes - Marseille

Marseille, Provence-Alpes-Côte d'Azur Region, 13273, France

Location

Centre Antoine Lacassagne

Nice, Provence-Alpes-Côte d'Azur Region, 06189, France

Location

Hôpital Henri Mondor

Créteil, Île-de-France Region, 94010, France

Location

Gustave Roussy - Departement Oncologie-Radiotherapie

Villejuif, Île-de-France Region, 94805, France

Location

Universitätsklinikum Münster

Münster, North Rhine-Westphalia, 48149, Germany

Location

Universitätsmedizin der Johannes Gutenberg, Universität Mainz

Mainz, Rhineland-Palatinate, 55101, Germany

Location

Pamela Youde Nethersole Eastern Hospital

Chai Wan, Hong Kong Island, 00000, Hong Kong

Location

Tuen Mun Hospital

Tuenmen, Hong Kong Island, 00000, Hong Kong

Location

Prince of Wales Hospital

Hong Kong, Hong Kong SAR, 00000, Hong Kong

Location

Queen Mary Hospital

Hong Kong, Hong Kong SAR, 00000, Hong Kong

Location

Hong Kong Integrated Oncology Centre (HKIOC)

Central, 0, Hong Kong

Location

Semmelweis University

Budapest, 1083, Hungary

Location

Jasz-Nagykun-Szolnok Varmegyei Hetenyi Geza Korhaz

Szolnok, 5000, Hungary

Location

Lady Davis Carmel Medical Center

Haifa, 3436212, Israel

Location

Tel- Aviv Sourasky Medical Center - Nephrology

Tel Aviv, 6423906, Israel

Location

University Hospital Of Ferrara - Oncologia Clinica

Ferrara, Emilia-Romagna, 44124, Italy

Location

Azienda Ospedaliero Universitaria di Modena_Policlinico - Oncologia

Modena, Emilia-Romagna, 41124, Italy

Location

Azienda Ospedaliero Universitaria Parma - SC Oncologia Medica

Parma, Emilia-Romagna, 43126, Italy

Location

Centro di Riferimento Oncologico di Aviano - Oncologia Medica e dei Tumori Immuno-Correlati

Aviano, Friuli Venezia Giulia, 33081, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Servizio di Radioterapia Oncologica

Rome, Lazio, 00168, Italy

Location

Ente Ospedaliero Ospedali Galliera Di Genova - Oncologia Medica

Genoa, Liguria, 16128, Italy

Location

Istituto Europeo di Oncologia s.r.l

Milan, Lombardy, 20141, Italy

Location

Azienda Ospedaliero-Universitaria Ss.Antonio E Biagio E C.Arrigo Alessandria_Presidio Civile - Oncologia

Alessandria, Piedmont, 15121, Italy

Location

Azienda Provinciale Per I Servizi Sanitari_Ospedale Santa Chiara - UO Oncologia Medica

Trento, Trentino-Alto Adige, 38122, Italy

Location

Istituto Oncologico Veneto_Padova - UOC Oncologia 1

Padova, Veneto, 35128, Italy

Location

The Hospital of Lithuanian University of Health SciencesLUHS

Kaunas, LT-50009, Lithuania

Location

PI Klaipedos University Hospital

Klaipėda, LT-92288, Lithuania

Location

National Cancer Institute

Vilnius, LT-08660, Lithuania

Location

Vilnius University Hospital Santaros Klinikos

Vilnius, LT-08661, Lithuania

Location

Szpital Wojewodzki im. Mikolaja Kopernika w Koszalinie - Oddzial Dzienny Chemioterapii

Koszalin, 75-851, Poland

Location

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie

Krakow, 31-115, Poland

Location

Scanmed SA ZOZ Gastromed

Lublin, 20-582, Poland

Location

Szpital Grochowski im. dr.med. Rafala Masztaka

Warsaw, 04-073, Poland

Location

Uniwersytecki Szpital Kliniczny UM we Wroclawiu

Wroclaw, 50-556, Poland

Location

Chelyabinsk Regional Oncology Dispensary

Chelyabinsk, 454087, Russia

Location

National Medical Research Radiology Center

Obninsk, 249036, Russia

Location

National Cancer Center Singapore - Oncology Department

Singapore, 168583, Singapore

Location

Singapore General Hospital

Singapore, 169608, Singapore

Location

National Cancer Center

Goyang-si, Gyeonggido, 10408, South Korea

Location

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggido, 13620, South Korea

Location

Seoul St. Mary's Hospital

Seoul, Seocho-Gu, 6591, South Korea

Location

Asan Medical Center | Ophthalmology

Seoul, Seoul Teugbyeolsi, 05505, South Korea

Location

Seoul National University Hospital

Seoul, Seoul Teugbyeolsi, 3080, South Korea

Location

Complexo Hospitalario Universitario De Santiago | Oncologia

Santiago de Compostela, A Coruña, 15706, Spain

Location

Hospital Universitari Son Espases | Oncologia

Palma de Mallorca, Balearic Islands, 7120, Spain

Location

Hospital Germans Trias I Pujol | Oncologia

Badalona, Barcelona, 08916, Spain

Location

Hospital General Universitario De Castellon | Oncologia

Castellon, Castellón, 12002, Spain

Location

Hospital Universitario Puerta De Hierro De Majadahonda | Oncologia

Majadahonda, Madrid, 28222, Spain

Location

Hospital Universitario Central De Asturias | Oncologia

Oviedo, Principality of Asturias, 33011, Spain

Location

Fundacion Centro Oncologico Regional De Galicia Jose Antonio Quiroga Y Pineyro | Oncologia

A Coruña, 15009, Spain

Location

Hospital Universitari Vall D Hebron | Oncologia

Barcelona, 08035, Spain

Location

Institut Catala D'oncologia | Girona | Oncologia

Barcelona, 08908, Spain

Location

Hospital De La Santa Creu I Sant Pau | Oncologia

Barcelona, 8041, Spain

Location

Hospital Universitario Puerta Del Mar | Oncologia

Cadiz, 11009, Spain

Location

Hospital Universitario De Jaen | Oncologia

Jaén, 23007, Spain

Location

Hospital Universitario Lucus Augusti | Oncologia

Lugo, 27003, Spain

Location

Hospital Universitario 12 De Octubre | Oncologia

Madrid, 28041, Spain

Location

Hospital Universitario Virgen De La Victoria | Oncologia

Málaga, 29010, Spain

Location

Fundacion Instituto Valenciano De Oncologia | Oncologia

Valencia, 46009, Spain

Location

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, 807377, Taiwan

Location

Taichung Veterans General Hospital

Taichung, 40705, Taiwan

Location

National Cheng Kung University Hospital

Tainan, 704, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

Chang Gung Memorial Hospital at Linkou

Taoyuan, 33305, Taiwan

Location

Baskent Universitesi Seyhan Hastanesi

Adana, 1250, Turkey (Türkiye)

Location

Hacettepe Universitesi Tip Fakultesi

Ankara, 06230, Turkey (Türkiye)

Location

Ankara Yildirim Beyazit Universitesi Tip Fakültesi

Ankara, 6050, Turkey (Türkiye)

Location

Ankara Universitesi Tip Fakultesi Hastanesi

Ankara, 6100, Turkey (Türkiye)

Location

Trakya Univ. Tip Fak.

Edirne, 22030, Turkey (Türkiye)

Location

Gaziantep Universitesi Tip Fakultesi

Gaziantep, 27070, Turkey (Türkiye)

Location

Istanbul Universitesi Istanbul Tip Fakultesi Hastanesi

Istanbul, 34093, Turkey (Türkiye)

Location

Istanbul Egitim ve Arastirma Hastanesi

Istanbul, 34098, Turkey (Türkiye)

Location

Istanbul Universitesi Cerrahpasa-Cerrahpasa Tip Fakultesi

Istanbul, 34098, Turkey (Türkiye)

Location

TC Saglik Bakanligi Goztepe ProfDr Suleyman Yalcin Sehir Has

Istanbul, 34722, Turkey (Türkiye)

Location

Medipol Universitesi Tip Fakultesi

Istanbul, 34810, Turkey (Türkiye)

Location

Marmara University Medical Faculty | Pediatric Nephrology

Istanbul, 34899, Turkey (Türkiye)

Location

Ege Universitesi Tip Fakultesi Hastanesi

Izmir, 35100, Turkey (Türkiye)

Location

Izmir Tepecik Egitim ve Arastirma Hastanesi

Izmir, 35180, Turkey (Türkiye)

Location

Dokuz Eylul Universitesi Arastirma Uygulama Hastanesi

Izmir, 35330, Turkey (Türkiye)

Location

Izmir Ekonomi Universitesi Medikal Point Hastanesi

Izmir, 35575, Turkey (Türkiye)

Location

Erciyes Universitesi Tip Fakultesi

Kayseri, 38039, Turkey (Türkiye)

Location

Mersin Universitesi Tip Fakultesi

Mersin, 33079, Turkey (Türkiye)

Location

Ondokuz Mayis Universitesi Tip Fakultesi Saglik Uygulama ve Arastirma Merkezi

Samsun, 55139, Turkey (Türkiye)

Location

Royal Berkshire NHS Foundation Trust¦Royal Berkshire Hospital - Oncology

Reading, Berkshire, RG1 5AN, United Kingdom

Location

NHS Greater Glasgow & Clyde | Beatson West of Scotland Cancer Centre - Clinical Research Unit

Glasgow, Scotland, G12 0YN, United Kingdom

Location

MeSH Terms

Interventions

radium Ra 223 dichloride

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2020
• First Posted: October 22, 2020
• Study Start: November 9, 2020
• Primary Completion: November 21, 2025
• Study Completion (Estimated): October 12, 2026
• Last Updated: June 8, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

HK (5); CZ (7); TW (5); GB (2); ES (16); LI (4); IT (10); RU (2); FR (13); DE (2); AU (2); FI (4); HU (2); IL (2); SG (2); PL (5); KR (5); TU (19)