Denosumab in Combination With Enzalutamide in Progressive Metastatic Castrate-resistant Prostate Cancer and Bone Metastases.

Exclusion criteria

• ✕. Patients should not be receiving any other investigational agents for the treatment of prostate cancer or other diseases (within 30 days prior to registration).
• ✕. Patients with GI tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's disease, ulcerative colitis).
• ✕. Have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, or stable chronic liver disease per investigator assessment).
• ✕. Prior therapy with orteronel, ketoconazole, aminoglutethimide, abiraterone or enzalutamide, denosumab or radium 223.
• ✕. All anti-androgen therapy (including bicalutamide) is excluded within 6 weeks prior to first dose of study drug. Any other therapies for prostate cancer, other than GnRH analogue therapy, such as progesterone, medroxyprogesterone, progestins (megesterol), or 5-alpha reductase inhibitors (eg, finasteride or dutasteride), must be discontinued 2 weeks before the first dose of study drug. No prior bisphosphonates/Rank ligand inhibitors are allowed except when administered for bone density preservation in association with androgen deprivation therapy.
• ✕. Prior chemotherapy for prostate cancer, with the exception of:
• ✕. Diagnosis of or treatment for another systemic malignancy within 2 years before the first dose of study drug, or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
• ✕. History of myocardial infarction, unstable symptomatic ischemic heart disease/ unstable angina, uncontrolled on-going arrhythmias of Grade \>2 (National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5), pulmonary embolism, or any other cardiac condition (e.g. pericardial effusion restrictive cardiomyopathy) within 6 months prior to first dose of study drug. Patients with long QT, QTcF \>470ms or uncontrolled hypertension are excluded.