Prostate Carcinoma Metastatic to the Bone
Conditions
Brief summary
This is an open label study designed to examine the effects of Enzalutamide with concurrent administration of Radium Ra 223 dichloride in Castrate-Resistant (Hormone-Refractory) Prostate Cancer subjects with symptomatic bone metastases in both the pre- and post-chemotherapy setting.
Detailed description
This is an open label study designed to examine the effects of Enzalutamide with concurrent administration of Radium Ra 223 dichloride in castrate resistant (hormone-refractory) prostate cancer subjects with symptomatic bone metastasis, in both the pre- and post- chemotherapy setting. Radium Ra 223 dichloride is approved by the US Food and Drug Administration for this indication. Enzalutamide is US Food and Drug Administration approved for this indication. Approximately 40 subjects will be enrolled to obtain 30 evaluable subjects. All subjects will receive Radium Ra 223 dichloride every 4 weeks for a total of 6 doses over 24 weeks and concurrent Enzalutamide for a minimum duration of 24 weeks. The sponsor will provide Enzalutamide after the End of Treatment visit until the last Long Term Follow Up visit has been completed. Subjects will continue to receive Enzalutamide as long as a positive response to therapy is demonstrated. Enzalutamide may be discontinued at any time per physician discretion. Subjects will be evaluated 30 days after the last dose of Radium Ra 223 dichloride. Including screening, the total duration of the study is 32 weeks plus every 3 month follow up visits while subjects are receiving Enzalutamide.
Interventions
DRUGEnzalutamide
used concomitantly
RADIATIONRadium ra 223 dichloride
Sponsors
Astellas Pharma Inc
Carolina Research Professionals, LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Eligible subjects will conform to all of the inclusion criteria listed below: 1. Subject must be able to understand and be willing to sign the written Informed Consent Form. A signed IRB approved Informed Consent Form must be appropriately obtained prior to the conduct of any study-specific procedure. 2. Subject is willing and able to comply with the protocol, including all study visits and procedures. 3. Subject is a male, greater than 18 years at time of enrollment. 4. Life expectancy of at least 9 months. 5. Subject has histologically documented prostate cancer confirmed by a pathology report from a prostate biopsy or radical prostatectomy specimen. 6. Subject must: 1\. have initiated a stable dose of daily Enzalutamide within 45 days of enrollment (Cycle 1/Week 1/ Day 1), or 2. plans to initiate a stable daily dose of Enzalutamide within 30 days of the first Radium Ra 223 dichloride treatment. 7\. Subject must plan to receive all 6 Radium Ra 223 dichloride injections and daily oral doses of Enzalutamide during the study, per protocol. 8\. Subject has a history of bone metastasis from prostate cancer as evidenced by imaging performed within 90 days of enrollment (Cycle 1/Week 1/Day 1) from one of the following: 1\. Tc Bone Scan or 2. Sodium Fluoride PET/CT Scan * If a bone scan is used, solitary lesions which could be contributed to causes other than prostate cancer must be confirmed with a second modality (i.e.: plain films, CT scan or MRI). 9\. Subject has Castrate Resistant Prostate Cancer, defined as having a rising PSA level and a testosterone level \</= 50ng/dl (2.0 nM/L) while receiving androgen deprivation therapy (medical or surgical castration). Subject must also plan to receive androgen deprivation therapy throughout the study. * PSA progression is defined as having at least 2 rising PSA levels taken at least 7 days apart, with the 2nd PSA being 2.0 ng/dl or greater. 10\. Subject has the presence of cancer related bone pain requiring treatment with analgesic medications (including but not limited to acetaminophen, NSAIDS, Cox-2 inhibitors, and narcotic opioids). 11\. Subject has an ECOG performance status of 0-2 at the screening and enrollment visits. 12\. Acceptable hematology and serum biochemistry screening values: White Blood Cell (WBC) \>/= 3,000/mm3 Absolute Neutrophil Count (ANC) \>1500/mm3 Platelet (PLT) count \>100,000/mm3 Hemoglobin (HGB) \> 10.0 g/dL (100g/L; 6.2 mmol/L Creatinine \<1.5 ULN Total bilirubin level \<1.5 X ULN Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<2.5 X ULN albumin \>25 g/L Baseline electrolytes within normal limits ( Sodium, potassium, chloride, calcium, phosphate, magnesium, LDH, γGT, urea, total protein) 13\. Normal Liver Function Tests (LFT) and normal Renal Function Tests (RFT) at the screening visit. If the subject has LFT's or RFT's greater than 2.5 times the upper limit of normal (ULN), Medical Monitor review, in conjunction with the subject's PI, will be required. 14\. Subjects receiving Anti-Resorptive medications, such as denosumab (XGEVA) and Zolendronic Acid (Zometa), must be on a stable dose for at least 90 days prior to enrollment (Cycle 1/Week 1/Day 1). Anti-resorptive medications may be not be added to the subject's regimen during the study. Anti-resorptive discontinuation will be allowed per Investigator discretion due to adverse events attributable to that medication. 15\. Subjects of childbearing potential must agree to use adequate contraception beginning at the enrollment until at least 30 days after the last dose of the study drugs. The definition of adequate contraception will be based on the judgment of the principal investigator or a designated associate.
Exclusion criteria
Eligible subjects must not meet any of the
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of participants with adverse events and serious adverse events . Adverse events deemed to be related to either study medication will be followed until resolution. | 30 days after the last cycle of Radium Ra 223 dichloride, which will be approximately 7 months after study enrollment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quality of Life Questionnaire | Thorughout the study and through the last follow-up visit, estimated to be 30 months after study enrollment | — |
| Time to measurable disease progression | Thorughout the study and through the last follow-up visit, estimated to be 30 months after study enrollment | — |
| Time to implementation of palliative radiotherapy | Thorughout the study and through the last follow-up visit, estimated to be 30 months after study enrollment | — |
| Time to analgesic (Opioid) advancements | Thorughout the study and through the last follow-up visit, estimated to be 30 months after study enrollment | — |
| Bone pain measured by the Bone Pain Index- Short Form questionnaire | Thorughout the study and through the last follow-up visit, estimated to be 30 months after study enrollment | Bone Pain |
| Changes and time to total-ALP progression will be measured by recording laboratory values | Thorughout the study and through the last follow-up visit, estimated to be 30 months after study enrollment | Changes and time to total-ALP progression |
| Progression to additional antineoplastic therapy will be measured by tracking subject diaries and concomitant medications | Thorughout the study and through the last follow-up visit, estimated to be 30 months after study enrollment | Progression to additional antineoplastic therapy |
| Performance status change will be measured by ECOG status | Thorughout the study and through the last follow-up visit, estimated to be 30 months after study enrollment | Performance status change |
| Time from start of Enzalutamide to PSA progression | Thorughout the study and through the last follow-up visit, estimated to be 30 months after study enrollment | — |
Countries
United States
Outcome results
None listed