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

Phase 4

Active, not recruiting

• Conditions: Metastatic Castrate Resistant Prostate Cancer (mCRPC)
• Interventions: Drug: Radium-223 dichloride (Xofigo, BAY88-8223); Drug: NAH therapy

• Registration Number: NCT04597125
• Lead Sponsor: Bayer

Brief Summary

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations
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Related News

Study Timeline

• Study First Submitted: 2020-10-16
• Study First Submitted QC: 2020-10-16
• Study First Posted: 2020-10-22
• Study Start: 2020-11-09
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-20
• Last Update Posted: 2024-12-24
• Primary Completion: 2025-05-01
• Study Completion: 2026-05-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Male
• Target Recruitment: 696

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A	Radium-223 dichloride (Xofigo, BAY88-8223)	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
Arm B	NAH therapy	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)

Primary Outcome Measures

Name	Time	Method
Overall survival (OS)	Up to five years

Secondary Outcome Measures

Name	Time	Method
Time to first symptomatic skeletal event (SSE)	Up to five years
Time to pain progression (BPI-SF)	Up to five years	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.
Incidence of fractures	Up to five years
Time to deterioration of FACT-P total score	Up to five years	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.
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
Radiological Progression-free survival (rPFS)	Up to five years	rPFS is defined as the time from the date of randomization to the date of confirmed radiological progression or death, whichever occurs first.

Trial Locations

Locations (118)

A.O.U. di Modena - Policlinico; 🇮🇹 Modena, Emilia-Romagna, Italy

Azienda Ospedaliero Universitaria Parma - SC Oncologia Medica; 🇮🇹 Parma, Emilia-Romagna, Italy

Centro di Riferimento Oncologico di Aviano; 🇮🇹 Pordenone, Friuli-Venezia Giulia, Italy

Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Servizio di Radioterapia Oncologica; 🇮🇹 Roma, Lazio, Italy

E.O. Ospedali Galliera; 🇮🇹 Genova, Liguria, Italy

Istituto Europeo di Oncologia s.r.l; 🇮🇹 Milano, Lombardia, Italy

A.O. Nazionale SS Antonio e Biagio e Cesare Arrigo - Oncologia; 🇮🇹 Alessandria, Piemonte, Italy

APSS Trento; 🇮🇹 Trento, Trentino-Alto Adige, Italy

Istituto Oncologico Veneto_Padova - UOC Oncologia 1; 🇮🇹 Padova, Veneto, Italy

Ciutat Sanitaria i Universitaria de la Vall d'Hebron; 🇪🇸 Barcelona, Spain

Hospital de la Santa Creu i Sant Pau | Gynecology Department; 🇪🇸 Barcelona, Spain

Consorcio Hospitalario Provincial de Castellón; 🇪🇸 Castellón, Spain

I.C.O Girona; 🇪🇸 Girona, Spain

Complejo Hospitalario de Jaén; 🇪🇸 Jaén, Spain

Hospital Lucus Augustí; 🇪🇸 Lugo, Spain

Hospital Universitario 12 de Octubre; 🇪🇸 Madrid, Spain

Vseobecna fakultni nemocnice v Praze; 🇨🇿 Praha 2, Czechia

Fakultní nemocnice Bulovka; 🇨🇿 Praha 8, Czechia

Docrates Klinikka; 🇫🇮 Helsinki, Finland

Urocentrum Praha, s.r.o.; 🇨🇿 Praha 2, Czechia

Specialist Services Medical Group; 🇦🇺 Castle Hill, New South Wales, Australia

Gosford Hospital; 🇦🇺 Gosford, New South Wales, Australia

North West Cancer Centre; 🇦🇺 North Tamworth, New South Wales, Australia

Northern Cancer Institute; 🇦🇺 St Leonards, New South Wales, Australia

Prince of Wales Hospital NSW; 🇦🇺 Sydney, New South Wales, Australia

Illawarra Shoalhaven Local Health District; 🇦🇺 Wollongong, New South Wales, Australia

Icon Cancer Care; 🇦🇺 Brisbane, Queensland, Australia

Tasman Health Care; 🇦🇺 Southport, Queensland, Australia

The Tweed Hospital; 🇦🇺 Tugun, Queensland, Australia

Royal Adelaide Hospital; 🇦🇺 Adelaide, South Australia, Australia

Nepean Hospital; 🇦🇺 Kingswood, Australia

Kepler Universitätsklinikum Campus III; 🇦🇹 Linz, Oberösterreich, Austria

Klinik Ottakring - Wilhelminenspital; 🇦🇹 Wien, Austria

Fakultni nemocnice u sv. Anny; 🇨🇿 Brno, Czechia

Nemocnice Chomutov, o.z.; 🇨🇿 Chomutov, Czechia

Krajska Nemocnice Liberec; 🇨🇿 Liberec, Czechia

Fakultni Thomayerova Nemocnice; 🇨🇿 Prague, Czechia

Oulun yliopistollinen sairaala; 🇫🇮 Oulu, Finland

Seinäjoen keskussairaala; 🇫🇮 Seinäjoki, Finland

Tampereen yliopistollinen sairaala; 🇫🇮 Tampere, Finland

Hôpital Saint André - Bordeaux; 🇫🇷 Bordeaux, France

Hôpital Morvan - Brest; 🇫🇷 Brest, France

Centre de Lutte Contre le Cancer François Baclesse; 🇫🇷 Caen Cedex 5, France

Hôpital Henri Mondor; 🇫🇷 Creteil, France

Centre Georges Francois Leclerc Dijon; 🇫🇷 Dijon, France

Centre Hospitalier Universitaire - Grenoble; 🇫🇷 Grenoble, France

Institut Paoli-Calmettes - Marseille; 🇫🇷 Marseille, France

Centre Antoine Lacassagne; 🇫🇷 Nice Cedex 2, France

Institut de Cancérologie Jean Godinot; 🇫🇷 Reims, France

Centre Eugène Marquis - Rennes Cedex; 🇫🇷 Rennes Cedex, France

CHU STRASBOURG - Hôpital de Hautepierre; 🇫🇷 Strasbourg, France

Institut de Cancérologie de Lorraine - Alexis Vautrin; 🇫🇷 Vandoeuvre-les-Nancy, France

Institut Gustave Roussy - Département de Médecine Oncologique; 🇫🇷 Villejuif Cedex, France

Universitaetsklinikum Muenster; 🇩🇪 Münster, Nordrhein-Westfalen, Germany

Universitätsmedizin der Johannes Gutenberg Universität Mainz; 🇩🇪 Mainz, Rheinland-Pfalz, Germany

Hong Kong Integrated Oncology Centre (HKIOC); 🇭🇰 Central, Hong Kong

Pamela Youde Nethersole Eastern Hospital; 🇭🇰 Chai Wan, Hong Kong

Prince of Wales Hospital; 🇭🇰 Hong Kong, Hong Kong

Queen Mary Hospital; 🇭🇰 Hong Kong, Hong Kong

Tuen Mun Hospital; 🇭🇰 TBC, Hong Kong

Semmelweis University; 🇭🇺 Budapest, Hungary

Jasz-Nagykun-Szolnok Varmegyei Hetenyi Geza Korhaz; 🇭🇺 Szolnok, Hungary

Lady Davis Carmel Medical Center; 🇮🇱 Haifa, Israel

Tel-Aviv Sourasky Medical Center; 🇮🇱 Tel Aviv, Israel

A.O.U. di Ferrara; 🇮🇹 Ferrara, Emilia-Romagna, Italy

National Cancer Center; 🇰🇷 Goyang-si, Gyeonggido, Korea, Republic of

Seoul National University Bundang Hospital; 🇰🇷 Seongnam-si, Gyeonggido, Korea, Republic of

Seoul St. Mary's Hospital; 🇰🇷 Seoul, Seocho-Gu, Korea, Republic of

Seoul National University Hospital; 🇰🇷 Seoul, Seoul Teugbyeolsi, Korea, Republic of

Asan Medical Center; 🇰🇷 Seoul, Korea, Republic of

The Hospital of Lithuanian University of Health SciencesLUHS; 🇱🇹 Kaunas, Lithuania

PI Klaipedos University Hospital; 🇱🇹 Klaipeda, Lithuania

National Cancer Institute; 🇱🇹 Vilnius, Lithuania

Vilnius University Hospital Santaros Klinikos; 🇱🇹 Vilnius, Lithuania

Szpital Wojewodzki im. Mikolaja Kopernika w Koszalinie - Oddzial Dzienny Chemioterapii; 🇵🇱 Koszalin, Poland

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie; 🇵🇱 Krakow, Poland

Scanmed SA ZOZ Gastromed; 🇵🇱 Lublin, Poland

Szpital Grochowski im. dr.med. Rafala Masztaka; 🇵🇱 Warszawa, Poland

Uniwersytecki Szpital Kliniczny UM we Wroclawiu; 🇵🇱 Wroclaw, Poland

Chelyabinsk Regional Oncology Dispensary; 🇷🇺 Chelyabinsk, Russian Federation

National Medical Research Radiology Center; 🇷🇺 Obninsk, Russian Federation

National Cancer Center Singapore; 🇸🇬 Singapore, Singapore

Singapore General Hospital; 🇸🇬 Singapore, Singapore

Hospital Clínico Universitario de Santiago de Compostela; 🇪🇸 Santiago de Compostela, A Coruña, Spain

Hospital Universitario Puerta del Mar; 🇪🇸 Cadiz, Andalucía, Spain

Hospital Central de Asturias; 🇪🇸 Oviedo, Asturias, Spain

Hospital Universitari Germans Trias i Pujol; 🇪🇸 Badalona, Barcelona, Spain

Hospital Universitari Son Espases; 🇪🇸 Palma De Mallorca, Illes Baleares, Spain

Hospital Universitario Clinica Puerta de Hierro; 🇪🇸 Majadahonda, Madrid, Spain

Hospital Universitario Virgen de la Victoria | Cardiology Department; 🇪🇸 Malaga, Málaga, Spain

Centro Oncológico de Galicia; 🇪🇸 A Coruña, Spain

Instituto Valenciano de Oncología; 🇪🇸 Valencia, Spain

Kaohsiung Medical University Chung-Ho Memorial Hospital; 🇨🇳 Kaohsiung City, Kaohsiung, Taiwan

Taichung Veterans General Hospital; 🇨🇳 Taichung, Taiwan

National Cheng Kung University Hospital; 🇨🇳 Tainan, Taiwan

Taipei Veterans General Hospital; 🇨🇳 Taipei, Taiwan

Chang Gung Memorial Hospital at Linkou; 🇨🇳 Taoyuan, Taiwan

Baskent Universitesi Seyhan Hastanesi; 🇹🇷 Adana, Turkey

Ankara Yildirim Beyazit Universitesi Tip Fakültesi; 🇹🇷 Ankara, Turkey

Ankara Universitesi Tip Fakultesi Hastanesi; 🇹🇷 Ankara, Turkey

Hacettepe Universitesi Tip Fakultesi; 🇹🇷 Ankara, Turkey

Trakya Univ. Tip Fak.; 🇹🇷 Edirne, Turkey

Gaziantep Universitesi Tip Fakultesi; 🇹🇷 Gaziantep, Turkey

Istanbul Universitesi Istanbul Tip Fakultesi; 🇹🇷 Istanbul, Turkey

Istanbul Egitim ve Arastirma Hastanesi; 🇹🇷 Istanbul, Turkey

Istanbul Universitesi Cerrahpasa-Cerrahpasa Tip Fakultesi; 🇹🇷 Istanbul, Turkey

TC Saglik Bakanligi Goztepe ProfDr Suleyman Yalcin Sehir Has; 🇹🇷 Istanbul, Turkey

Medipol Universitesi Tip Fakultesi; 🇹🇷 Istanbul, Turkey

Marmara University Medical Faculty | Pediatric Nephrology; 🇹🇷 Istanbul, Turkey

Dokuz Eylul Universitesi Tip Fakultesi; 🇹🇷 Izmir, Turkey

Ege Universitesi Tip Fakultesi; 🇹🇷 Izmir, Turkey

Izmir Tepecik Egitim ve Arastirma Hastanesi; 🇹🇷 Izmir, Turkey

Izmir Ekonomi Universitesi Medikal Point Hastanesi; 🇹🇷 Izmir, Turkey

Erciyes Universitesi Tip Fakultesi; 🇹🇷 Kayseri, Turkey

Mersin Universitesi Tip Fakultesi; 🇹🇷 Mersin, Turkey

Ondokuz Mayis Uni Tip Fakultesi; 🇹🇷 Samsun, Turkey

Royal Berkshire Hospital; 🇬🇧 Reading, Berkshire, United Kingdom

Beatson West of Scotland Cancer Centre; 🇬🇧 Glasgow, United Kingdom