Radium-223 is indicated for the treatment of patients with mCRPC with symptomatic bone metastases and no known visceral metastatic disease. However, very few data have been reported in patients with mCRPC who are asymptomatic or mildly symptomatic. Recently, results from an International Expanded Access Program have also suggested a benefit of radium-223 in asymptomatic patients with mCRPC. In addition, the mechanism of action of radium-223 should not be correlated with the presence/absence of the AR-V7 mutation, although this issue has not yet been evaluated. The aim of this study is to assess the efficacy of radium-223 in asymptomatic patients with mCRPC, and to establish the association between AR-V7 status and radium-223 activity.
Primary objective: To assess the efficacy of radium-223 in asymptomatic patients with mCRPC who have progressed while on abiraterone acetate or enzalutamide treatment. Primary endpoint: To determine the efficacy of radium-223 in terms of radiological rPFS. Secondary objectives: * Safety profile. * To determine the association between AR-V7 status (positive vs. negative) and PFS. * To establish the relationship between CTCs number with radium-223 efficacy. Secondary endpoints: Safety AEs will be evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) of the US National Cancer Institute (NCI) version 4.0 \[20\]. Grade 3 or 4 AEs and serious adverse events (SAEs) will be assessed to determine the safety and tolerability of the various combinations of drugs. Efficacy * Radiographic progression-free survival (rPFS) depending on AR-V7 status. * Overall survival (OS). * Time to first symptomatic skeletal event (SSE). * Time to prostate specific antigen (PSA) progression according to the Alpharadin in Symptomatic Prostate Cancer (ALSYMPCA) study criteria. * Determination percentage of PSA progression. * Alkaline phosphatase level response (AF), normalization of alkaline phosphatase level, according to the ALSYMPCA study criteria. Molecular aspects * Assessment of AR-V7 mutation evolution during the study treatment. * Determination changes in CTCs number during the study treatment.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
52
Radium-223 at a dose of 55 kBq
MedSIR Investigative site
Barcelona, Spain
MedSIR Investigative site
Cáceres, Spain
MedSIR Investigative site
Córdoba, Spain
MedSIR Investigative site
Lugo, Spain
MedSIR Investigative site
Madrid, Spain
MedSIR investigative site
Palma de Mallorca, Spain
Assess the Efficacy of Radium-223 in Terms of Radiological rPFS
The primary efficacy endpoint is the median PFS (evaluated using RECIST v1.1) achieved with radium-223 treatment
Time frame: From date of first drug administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 20 months
AEs and Serious Adverse Events (SAEs)
Time frame: Starting from the first procedure required by the study up to three months after study discontinuation.
Radiographic Progression-free Survival (rPFS) Depending on AR-V7 Status.
Time frame: From date of inclusion until Radiographic progression, assessed up to 20 months
Overall Survival (OS).
Time frame: From date of inclusion until death from any cause or the last date the patient was known to be alive, assessed up to 20 months.
Time to First Symptomatic Skeletal Event (SSE).
Time to first SSE defined as the time from treatment initiation until SSE (pathological fractures, vertebral or non-vertebral, spinal cord compression, radiation or surgery to bone). For all other events, the start date of the event/medication/therapy was used as the time of the event. If an event has not occurred at the time of the analysis or the patient has been lost to follow-up, the time-to-event variables will be censored at the last disease assessment date.
Time frame: From date of first drug administration until SSE, assessed up to 20 months
Time to PSA Progression According to the ALSYMPCA Study Criteria.
Time frame: From date of first study drug administration to when PSA progression is observed, assessed up to 20 months
PSA Progression
PSA progression (defined as PSA elevation ≥ 25% and ≥ 2 ng/mL after 12 weeks).
Time frame: From date of first study drug administration to when PSA progression is observed, assessed up to 20 months
Alkaline Phosphatase Level Response (AF), Normalization of Alkaline Phosphatase Level
Progression defined as FA elevation ≥ 25% after 12 weeks
Time frame: From date of first study drug administration until End of Treatment, assessed up to 6 months
Assessment of AR-V7 Mutation Evolution
Time frame: From date of first study drug administration until End of Treatment, assessed up to 6 months
Number of Participants With Change in CTCs Number
CTC levels will be measured at the start and at the end of the study. Patients will be categorized based on their CTC levels: those with a CTC count higher than 5, lower than 5, and CTC not reported. A lower CTC count is considered a better outcome.
Time frame: From date of first study drug administration until End of Treatment, assessed up to 6 months
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