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.
- 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
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.
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