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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04597125




Registration number
NCT04597125
Ethics application status
Date submitted
16/10/2020
Date registered
22/10/2020
Date last updated
7/05/2021

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
2019-000476-42
Secondary ID [2] 0 0
20510
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Castrate Resistant Prostate Cancer (mCRPC) 0 0
Condition category
Condition code
Cancer 0 0 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Radium-223 dichloride (Xofigo, BAY88-8223)
Treatment: Drugs - NAH therapy

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

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)


Treatment: Drugs: 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

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

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall survival (OS)
Timepoint [1] 0 0
Up to five years
Secondary outcome [1] 0 0
Time to first symptomatic skeletal event (SSE)
Timepoint [1] 0 0
Up to five years
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
Up to five years
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
Up to five years
Secondary outcome [4] 0 0
Adverse events assessments using NCI CTCAE (v5.0)
Timepoint [4] 0 0
After first administration of study intervention up to 30 days after the last dose of study intervention
Secondary outcome [5] 0 0
Incidence of fractures
Timepoint [5] 0 0
Up to five years
Secondary outcome [6] 0 0
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.
Timepoint [6] 0 0
Up to five years

Eligibility
Key inclusion criteria
- Participants who have histologically confirmed adenocarcinoma of the prostate.

- Participants with metastatic castrate resistant prostate cancer (mCRPC) progressing
on/after one line of novel anti-hormonal therapy (NAH) (after being treated for at
least 3 months) for metastatic prostate cancer (mHSPC and mCRPC).

- 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
Minimum age
18 Years
Maximum age
No limit
Gender
Males
Can healthy volunteers participate?
No
Key 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 5 mg
prednisone / prednisolone twice daily.

- Pathological finding consistent with tumors with 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

- Atrial fibrillation, or other cardiac arrhythmia requiring therapy

- 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 systemic radiotherapy with strontium-89, samarium-153, rhenium-186, rhenium-188,
or radium-223.

- 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA
Recruitment hospital [1] 0 0
Specialist Services Medical Group - Castle Hill
Recruitment hospital [2] 0 0
North West Cancer Centre - North Tamworth
Recruitment hospital [3] 0 0
Prince of Wales Hospital - Randwick
Recruitment hospital [4] 0 0
Northern Cancer Institute - St Leonards
Recruitment hospital [5] 0 0
Wollongong Private Hospital - Wollongong
Recruitment hospital [6] 0 0
The Wesley Hospital - Auchenflower
Recruitment hospital [7] 0 0
Icon Cancer Care - Brisbane
Recruitment hospital [8] 0 0
Tasman Health Care - Southport
Recruitment hospital [9] 0 0
The Tweed Hospital - Tugun
Recruitment hospital [10] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [11] 0 0
Calvary North Adelaide Hospital - North Adelaide
Recruitment hospital [12] 0 0
Nepean Hospital - Penrith
Recruitment postcode(s) [1] 0 0
2154 - Castle Hill
Recruitment postcode(s) [2] 0 0
2340 - North Tamworth
Recruitment postcode(s) [3] 0 0
2031 - Randwick
Recruitment postcode(s) [4] 0 0
2065 - St Leonards
Recruitment postcode(s) [5] 0 0
2500 - Wollongong
Recruitment postcode(s) [6] 0 0
4066 - Auchenflower
Recruitment postcode(s) [7] 0 0
4101 - Brisbane
Recruitment postcode(s) [8] 0 0
4215 - Southport
Recruitment postcode(s) [9] 0 0
4224 - Tugun
Recruitment postcode(s) [10] 0 0
5000 - Adelaide
Recruitment postcode(s) [11] 0 0
5006 - North Adelaide
Recruitment postcode(s) [12] 0 0
2757 - Penrith
Recruitment outside Australia
Country [1] 0 0
Austria
State/province [1] 0 0
Oberösterreich
Country [2] 0 0
Austria
State/province [2] 0 0
Wien
Country [3] 0 0
Czechia
State/province [3] 0 0
Brno
Country [4] 0 0
Czechia
State/province [4] 0 0
Chomutov
Country [5] 0 0
Czechia
State/province [5] 0 0
Liberec
Country [6] 0 0
Czechia
State/province [6] 0 0
Olomouc
Country [7] 0 0
Czechia
State/province [7] 0 0
Praha 2
Country [8] 0 0
Czechia
State/province [8] 0 0
Praha 4
Country [9] 0 0
Czechia
State/province [9] 0 0
Praha 8
Country [10] 0 0
Finland
State/province [10] 0 0
Helsinki
Country [11] 0 0
Finland
State/province [11] 0 0
Kuopio
Country [12] 0 0
Finland
State/province [12] 0 0
Oulu
Country [13] 0 0
Finland
State/province [13] 0 0
Seinäjoki
Country [14] 0 0
Finland
State/province [14] 0 0
Tampere
Country [15] 0 0
France
State/province [15] 0 0
Besancon
Country [16] 0 0
France
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Bordeaux Cedex
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France
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Bordeaux
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France
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Brest
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France
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Caen Cedex 5
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France
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Creteil
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France
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Dijon
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France
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Grenoble
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France
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Hyeres
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France
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Lille Cedex
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Lyon Cedex
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Marseille
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Montpellier Cedex
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France
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Nice Cedex 2
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France
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REIMS cedex
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France
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Rennes
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France
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Strasbourg
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France
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Toulouse Cedex 9
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France
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Tours
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France
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Vandoeuvre Les Nancy
Country [35] 0 0
France
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Villejuif Cedex
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Germany
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Nordrhein-Westfalen
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Germany
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Rheinland-Pfalz
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Germany
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Sachsen
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Germany
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Bremen
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Hong Kong
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Chai Wan
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Hong Kong
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Happy Valley
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Hong Kong
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Hong Kong
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Hong Kong
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Shatin
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Hungary
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Budapest
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Hungary
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Debrecen
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Szekszard
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Holon
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Lazio
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Liguria
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Lombardia
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Piemonte
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Italy
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Toscana
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Trentino-Alto Adige
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Italy
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Umbria
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Italy
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Veneto
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Korea, Republic of
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Gyeonggido
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Korea, Republic of
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Seoul
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Lithuania
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Kaunas
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Lithuania
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Klaipeda
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Lithuania
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Vilnius
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Poland
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Bydgoszcz
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Koszalin
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Krakow
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Warszawa
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Poland
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Wroclaw
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Russian Federation
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Chelyabinsk
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Russian Federation
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Moscow
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Russian Federation
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Obninsk
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Omsk
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Russian Federation
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Samara
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Tomsk
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Singapore
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Barcelona
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Illes Baleares
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Madrid
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A Coruña
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Spain
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Castellón
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Spain
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Málaga
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Spain
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Valencia
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Taiwan
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Kaohsiung
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Taiwan
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Taichung
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Taiwan
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Tainan
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Taiwan
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Taipei
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Taiwan
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Taoyuan
Country [92] 0 0
Turkey
State/province [92] 0 0
Adana
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Turkey
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Ankara
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Turkey
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Edirne
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Turkey
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Gaziantep
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Istanbul
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Izmir
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Kayseri
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Turkey
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Mersin
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Turkey
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Samsun
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United Kingdom
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Berkshire
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United Kingdom
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Lancashire
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United Kingdom
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Surrey
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United Kingdom
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Glasgow

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Bayer
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT04597125
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Bayer Clinical Trials Contact
Address 0 0
Country 0 0
Phone 0 0
(+)1-888-84 22937
Fax 0 0
Email 0 0
clinical-trials-contact@bayer.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04597125