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)

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.