Enzalutamide With or Without Radium Ra 223 Dichloride in Patients With Metastatic, Castration-Resistant Prostate Cancer
Castration-Resistant Prostate Carcinoma, Prostate Carcinoma Metastatic in the Bone, Stage IV Prostate Cancer
About this trial
This is an interventional treatment trial for Castration-Resistant Prostate Carcinoma
Eligibility Criteria
Inclusion Criteria:
- Men with metastatic, castration resistant prostate cancer involving the bone, which is symptomatic or asymptomatic
Castration resistance will be defined as the development of disease progression, defined as one of the following:
- Rising PSA x 2 values >= 2 weeks apart; minimum absolute PSA value 2 ng/mL
- Radiographic progression, with at least 1 new site of metastasis
- Symptomatic progression (ex: increase in pain despite stable imaging) AND despite ongoing luteinizing hormone-releasing hormone (LHRH) therapy OR testosterone level < 50
Men must have osseous metastases, but the presence of visceral metastases will not exclude patients from participation
- Prior external beam radiation therapy (> 4 weeks prior to enrollment) for palliation of osseous metastatic disease is allowed, provided there is at least one osseous metastasis which has not been irradiated and which can be biopsied
- No prior docetaxel or cabazitaxel chemotherapy for metastatic castration-resistant prostate cancer (mCRPC) (men treated with prior docetaxel administered as up-front therapy with androgen deprivation therapy [ADT] > 6 months ago will be eligible); prior abiraterone is allowed
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- Hemoglobin >= 9.5 g/dL
- Absolute neutrophil count >= 1,500
- Platelets >= 100,000
- Total bilirubin within normal institutional limits
- Creatinine clearance (calculated or measured) > 30 mL/min
- At least one risk factor predicting higher likelihood of bone marrow sample yield: elevated alkaline phosphatase, low hemoglobin, or elevated lactate dehydrogenase (LDH)
- Ability to understand and the willingness to sign a written informed consent
Exclusion Criteria:
- Prior treatment with docetaxel or cabazitaxel for mCRPC
Prior treatment with ARN-509 or enzalutamide (there is a grace period for men who wish to enroll and who have recently started enzalutamide for the first time but have taken less than 15 days of therapy)
- Concurrent use of androgen deprivation therapy aside from LHRH agonist or antagonist (i.e. bicalutamide, flutamide, nilutamide, abiraterone, ketoconazole, estrogen); there will be a 2 week wash-out period from the last dose of any of these agents until the first dose of enzalutamide on study; patients who have just started enzalutamide for fewer than 5 doses prior to enrollment in the trial are still considered eligible and not subject to wash-out
- Concurrent oral corticosteroid use aside from adrenal replacement, or use of other immunosuppressive agents (ex: infliximab); topical or inhaled steroids will be allowed
- Received systemic therapy with radionuclides (e.g., strontium-89, samarium- 153, rhenium-186, or rhenium-188, or radium Ra 223 dichloride) for the treatment of bony metastases
- History of seizures except for remote with specific etiology which has resolved (ex: alcohol induced seizure); transient ischemic attack (TIA) or cerebrovascular accident (CVA) within last 6 months
- Known untreated central nervous system (CNS) metastases; leptomeningeal disease will be an absolute exclusion criterion due to limited life expectancy
- Chronic diarrhea > grade 1, or a diagnosis of Crohn?s or ulcerative colitis
- Known hepatitis (hep) B or C, or known cirrhosis (screening for viral hepatitis is not required)
- Uncontrolled intercurrent illness such as infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness which would limit compliance with study requirements
- Imminent spinal cord compression based on clinical findings and/or magnetic resonance imaging (MRI); treatment should be completed for spinal cord compression
Sites / Locations
- City of Hope
- USC / Norris Comprehensive Cancer Center
- Cedars Sinai Medical Center
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Arm I (enzalutamide, radium 223)
Arm II (enzalutamide)
Patients receive enzalutamide PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive radium Ra 223 dichloride IV on day 1. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Patients receive enzalutamide as in Arm I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.