Radium-223 in Combination With Enzalutamide

Inclusion Criteria

• •1. Written informed consent obtained prior to any study-related procedures
• •2. Age ≥18 years and male.
• •3. ECOG performance status ≤ 2.
• •4. Histologically/cytologically confirmed adenocarcinoma of the prostate, and without neuroendocrine differentiation or small cell histology.
• •5. Metastatic disease as confirmed by Computed tomography (CT)/ Magnetic resonance imaging (MRI) or bone scan.
• •6. 6\. Patients must have documented Progressive disease (PD) either by radiographic or PSA criteria as defined in a) and b) below:
• •1. For the Radiographic PD assessment, 2 sets of scans using the same imaging modality (ie CT/MRI or bone scan) and taken at separate time points are required to document radiographic disease progression during or following the patient's most recent anti-neoplastic therapy, (note: the 1st bone scan can be from before most recent therapy but the 2nd scan must show disease progression during or after the most recent therapy).
• •For patients with bone disease, progression will be assessed following recommendations by the Prostate Cancer Working Group (PCWG2, see Appendix FC): appearance of 2 or more new lesions on bone scan, confirmed, if necessary, by other imaging modalities (such as CT scan or MRI), if results of the bone scans are ambiguous).
• •For patients with soft tissue lesions progression will be assessed using RECIST 1.1 criteria, (see Appendix GD). Patients may have measurable or non-measurable disease according to RECIST criteria version 1.1 (see Appendix GD)
• •2. PSA progression is defined as an increase in PSA, as determined by 2 separate measurements taken at least 1 week apart and confirmed by a third. If the third measurement is not greater than the second measurement, then a fourth measurement must be taken and must be greater than the second measurement for the patient to be eligible for the study. Furthermore, the confirmatory PSA measurement (i.e. the third or, if applicable, fourth PSA measurement) must be defined. If a patient has received prior anti-androgen therapy (e.g. bicalutamide), PSA progression must be evident and documented after discontinuation of anti-androgen therapy, (note: The 1st PSA reading taken to document disease progression when the patient presents can be while the patient is on Casodex or other ADT).
• •7. Prior surgical castration or concurrent use of an agent for medical castration with testosterone at screening less than 50ng/dL.
• •8. Screening PSA ≥ 2 ng/mL.
• •9. Patients, even if surgically sterilized who (i.e. status post-vasectomy):
• •* will abstain from intercourse
• •* or must agree to use barrier contraception during and for 6 months after discontinuation of study treatment.
• •* If the patient engages in sexual intercourse with a woman of childbearing potential, a condom and another form of birth control must be used during and for 6 months after treatment.
• •10. Stable medical condition
• •11. Life expectancy of 12 months or more based on general health and prostate cancer disease status as judged by the investigator.
• •12. Documented presence of osseous metastases with or without visceral involvement / lymph nodes.
• •13. Able to swallow study drug as whole tablet.
• •14. Adequate haematological, hepatic, and renal function.
• •15. Continuous daily use of oral prednisone, oral dexamethasone, or other systemic corticosteroids is allowed prior to study entry but must be discontinued a minimum of 2 weeks prior to start of study treatment.