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

Metastatic Castrate Resistant Prostate Cancer (mCRPC) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04597125
• Other study ID #: 20510
• Secondary ID: 2023-505830-89-0
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: November 9, 2020
• Est. completion date: May 1, 2025

Study information

• Verified date: June 2024
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 696
• Est. completion date: May 1, 2025
• Est. primary completion date: May 1, 2025
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Metastatic Castrate Resistant Prostate Cancer (mCRPC)
• Prostatic Neoplasms

Intervention

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

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Icon Cancer Care	Brisbane	Queensland
Australia	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	Nepean Hospital	Penrith
Australia	Prince of Wales Hospital NSW	Randwick	New South Wales
Australia	Tasman Health Care	Southport	Queensland
Australia	Northern Cancer Institute	St Leonards	New South Wales
Australia	The Tweed Hospital	Tugun	Queensland
Australia	Illawarra Shoalhaven Local Health District	Wollongong	New South Wales
Austria	Kepler Universitätsklinikum Campus III	Linz	Oberösterreich
Austria	Klinik Ottakring - Wilhelminenspital	Wien
Czechia	Fakultni nemocnice u sv. Anny	Brno
Czechia	Nemocnice Chomutov, o.z.	Chomutov
Czechia	Krajska Nemocnice Liberec	Liberec
Czechia	Fakultni Thomayerova Nemocnice	Prague
Czechia	Urocentrum Praha, s.r.o.	Praha 2
Czechia	Vseobecna fakultni nemocnice v Praze	Praha 2
Czechia	Fakultní nemocnice Bulovka	Praha 8
Finland	Docrates Klinikka	Helsinki
Finland	Oulun yliopistollinen sairaala	Oulu
Finland	Seinäjoen keskussairaala	Seinäjoki
Finland	Tampereen yliopistollinen sairaala, keskussairaala	Tampere
France	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
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
Germany	Universitätsmedizin der Johannes Gutenberg Universität Mainz	Mainz	Rheinland-Pfalz
Germany	Universitätsklinikum Münster (UKM)	Münster	Nordrhein-Westfalen
Hong Kong	Pamela Youde Nethersole Eastern Hospital	Chai Wan
Hong Kong	Queen Mary Hospital	Hong Kong
Hong Kong	Prince of Wales Hospital	Shatin
Hong Kong	Tuen Mun Hospital	TBC
Hungary	Semmelweis University	Budapest
Hungary	Jasz-Nagykun-Szolnok Varmegyei Hetenyi Geza Korhaz	Szolnok
Israel	Lady Davis Carmel Medical Center	Haifa
Israel	Tel-Aviv Sourasky Medical Center	Tel Aviv
Italy	A.O. Nazionale SS Antonio e Biagio e Cesare Arrigo - Oncologia	Alessandria	Piemonte
Italy	A.O.U. di Ferrara	Ferrara	Emilia-Romagna
Italy	E.O. Ospedali Galliera	Genova	Liguria
Italy	IRCCS Istituto Europeo di Oncologia s.r.l. (IEO)	Milano	Lombardia
Italy	A.O.U. di Modena - Policlinico	Modena	Emilia-Romagna
Italy	Istituto Oncologico Veneto IRCCS (IOV)	Padova	Veneto
Italy	A.O.U. di Parma	Parma	Emilia-Romagna
Italy	IRCCS Centro di Riferimento Oncologico (CRO)	Pordenone	Friuli-Venezia Giulia
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Roma	Lazio
Italy	APSS Trento	Trento	Trentino-Alto Adige
Korea, Republic of	National Cancer Center	Goyang-si	Gyeonggido
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggido
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul	Seoul Teugbyeolsi
Korea, Republic of	Seoul St. Mary's Hospital	Seoul
Lithuania	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
Poland	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
Russian Federation	Chelyabinsk Regional Oncology Dispensary	Chelyabinsk
Russian Federation	National Medical Research Radiology Center	Obninsk
Singapore	National Cancer Center Singapore	Singapore
Singapore	Singapore General Hospital	Singapore
Spain	Centro Oncológico de Galicia	A Coruña
Spain	Hospital Universitari Germans Trias i Pujol	Badalona (Barcelona)	Barcelona
Spain	Ciutat Sanitaria i Universitaria de la Vall d'Hebron	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau | Gynecology Department	Barcelona
Spain	Hospital Universitario Puerta del Mar	Cadiz	Andalucía
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	Hospital Universitario Clinica Puerta de Hierro	Majadahonda	Madrid
Spain	Hospital Universitario Virgen de la Victoria | Cardiology Department	Málaga
Spain	Hospital Central de Asturias	Oviedo	Asturias
Spain	Hospital Universitari Son Espases	Palma de Mallorca	Illes Baleares
Spain	Hospital Clínico Universitario de Santiago de Compostela	Santiago de Compostela	A Coruña
Spain	Instituto Valenciano de Oncología	Valencia
Taiwan	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
Turkey	Baskent Universitesi Seyhan Hastanesi	Adana
Turkey	Ankara Universitesi Tip Fakultesi Hastanesi	Ankara
Turkey	Ankara Yildirim Beyazit Universitesi Tip Fakültesi	Ankara
Turkey	Hacettepe Universitesi Tip Fakultesi	Ankara
Turkey	Trakya Univ. Tip Fak.	Edirne
Turkey	Gaziantep Universitesi Tip Fakultesi	Gaziantep
Turkey	Istanbul Egitim ve Arastirma Hastanesi	Istanbul
Turkey	Istanbul Universitesi Cerrahpasa-Cerrahpasa Tip Fakultesi	Istanbul
Turkey	Istanbul Universitesi Istanbul Tip Fakultesi	Istanbul
Turkey	Marmara Uni. Tip Fakultesi Pendik Egitim ve Aras. Hastanesi	Istanbul
Turkey	Medipol Universitesi Tip Fakultesi	Istanbul
Turkey	TC Saglik Bakanligi Goztepe ProfDr Suleyman Yalcin Sehir Has	Istanbul
Turkey	Dokuz Eylul Universitesi Tip Fakultesi	Izmir
Turkey	Ege Universitesi Tip Fakultesi	Izmir
Turkey	Izmir Ekonomi Universitesi Medikal Point Hastanesi	Izmir
Turkey	Izmir Tepecik Egitim ve Arastirma Hastanesi	Izmir
Turkey	Erciyes Universitesi Tip Fakultesi	Kayseri
Turkey	Mersin Universitesi Tip Fakultesi	Mersin
Turkey	Ondokuz Mayis Uni Tip Fakultesi	Samsun
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	Royal Berkshire Hospital	Reading	Berkshire

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Countries where clinical trial is conducted

Australia,  Austria,  Czechia,  Finland,  France,  Germany,  Hong Kong,  Hungary,  Israel,  Italy,  Korea, Republic of,  Lithuania,  Poland,  Russian Federation,  Singapore,  Spain,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival (OS)		Up to five years
Secondary	Time to first symptomatic skeletal event (SSE)		Up to five years
Secondary	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
Secondary	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
Secondary	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
Secondary	Incidence of fractures		Up to five years
Secondary	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

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