Management of Oligoprogressive Castration Resistant Prostate Cancer (PCS X)

Exclusion Criteria

• •Severe concurrent disease, infection, or co-morbidity that, in the judgment of the Investigator, would make the patient inappropriate for enrollment;
• •History of another malignancy within the previous 5 years other than curatively treated non-melanoma skin cancer;
• •Absolute neutrophil count \< 1,500/μL, platelet count \< 100,000/μL, or hemoglobin \< 5.6 mmol/L (9 g/dL) at the Screening visit (NOTE: patients may not have received any growth factors within 7 days or blood transfusions within 28 days of the hematologic laboratory values obtained at the Screening visit);
• •Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 2.5 times the upper limit of normal and total bilirubin \> 1.5 times the upper limit of normal at the Screening visit;
• •Creatinine \> 2 times the upper limit of normal at the Screening visit;
• •Clinically significant cardiovascular disease including:
• •1. Stroke or myocardial infarction within 6 months;
• •2. Uncontrolled angina within 6 months;
• •3. Coronary/peripheral artery bypass graft within 6 months;
• •4. Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or patients with history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram or multi-gated acquisition scan performed within three months results in a left ventricular ejection fraction that is ≥ 45%;
• •5. History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place;
• •6. Uncontrolled hypertension as indicated by a resting systolic BP ≥160 mmHg or diastolic BP ≥100 mmHg at screening. Patients may be re-screened after adjustments of antihypertensive medications;
• •7. Bradycardia as indicated by a heart rate of \< 50 beats per minute on the Screening ECG;
• •Gastrointestinal disorder or procedure which expects to interfere significantly with absorption (e.g., gastrectomy, active peptic ulcer disease within last 3 months);
• •Major surgery within 4 weeks of enrollment (Day 1 Visit);
• •Active viral hepatitis, active human immunodeficiency virus (HIV) or chronic liver disease
• •Use of opiate analgesics (eg. morphine, fentanyl, etc.) for pain from prostate cancer within 4 weeks of enrollment (Day 1 visit). This does not apply to non-morphine drugs like codeine;
• •Radiation therapy for treatment of the primary tumor within 3 weeks of enrollment (Day 1 visit);
• •Radiation or radionuclide therapy for treatment of metastasis;
• •Primary disease not treated;
• •Hormone naïve prostate cancer patients;
• •Treatment with estrogens or AR inhibitors (bicalutamide, flutamide, nilutamide, cyproterone acetate) within 4 weeks of enrollment (Day 1 visit);
• •Treatment with systemic biologic therapy for prostate cancer (other than approved bone targeted agents and GnRH-analogue therapy) or other agents with anti-tumour activity within 4 weeks of enrollment (Day 1 visit);
• •Prior use of an investigational agent that blocks androgen synthesis (e.g., abiraterone acetate, enzalutamide, Apalutamide, TAK-700, TAK-683, TAK-448) or targets the androgen receptor (e.g., BMS 641988) on clinical trials;
• •Known or suspected contraindications or hypersensitivity to darolutamide or GnRH agonists or any of the components of the formulations;
• •Use of an investigational agent within 4 weeks of enrollment (Day 1 visit);
• •Use of herbal products that may have hormonal anti-prostate cancer activity and/or are known to decrease PSA levels (e.g., saw palmetto) or systemic corticosteroids greater than the equivalent of 10 mg of prednisone per day within four weeks of enrollment (Day 1 visit);
• •Any condition or reason that, in the opinion of the Investigator, interferes with the ability of the patient to participate in the trial, which places the patient at undue risk, or complicates the interpretation of safety data;
• •Unable to swallow study medications and comply with study requirements
• •Known or suspected brain metastasis or active leptomeningeal disease;
• •\> 5 metastasis;
• •More than 4 metastasis in the same organ;
• •Patients considered for SBRT in previous history of radiation therapy to the same area.