Pharmacodynamic Study of Radium-223 in Men With Bone Metastatic Castration-Resistant Prostate Cancer
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|ClinicalTrials.gov Identifier: NCT02204943|
Recruitment Status : Completed
First Posted : July 31, 2014
Last Update Posted : June 8, 2018
This study will examine biomarkers involved in osteomimicry in bone metastases and circulating tumor cells (CTCs) of men with mCRPC before and during therapy with the bone-targeting radiopharmaceutical radium-223. This study will also examine the bio-distribution of radium-223 in bone and bone metastases of men with mCRPC.
The investigators hypothesize that bone metastases and CTCs in men with mCRPC will commonly express markers of EMT/plasticity and osteomimicry, not just in the normal surrounding osteoblastic stroma but in the epithelial tumor cells themselves and that radium-223 will target both of these compartments including the more mesenchymal/osteoblastic tumor cells and the surrounding osteoblasts in the active bone microenvironment, with a relative sparing of normal bone and bone marrow.
|Condition or disease||Intervention/treatment||Phase|
|Bone Metastatic Castration-Resistant Prostate Cancer||Device: Biomarker analysis Drug: Administration of radium-223||Early Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||Pharmacodynamic Study of Radium-223 in Men With Bone Metastatic Castration-Resistant Prostate Cancer|
|Actual Study Start Date :||May 6, 2015|
|Actual Primary Completion Date :||July 31, 2017|
|Actual Study Completion Date :||July 31, 2017|
|Experimental: Bone Biopsy and Circulating Tumor Cell Samples||
Device: Biomarker analysis
Pharmacodynamic study of Radium-223 in bone biopsy and circulating tumor cell samples
Drug: Administration of radium-223
Subjects will receive radium-223 treatment for their disease as standard of care in this protocol. They will be receiving this treatment regardless of their participation in this protocol.
- Proportion of patients who overexpress alkaline phosphatase (ALP) in Circulating Tumor Cells (CTCs) at each time point [ Time Frame: Cycle 1 Day 1, Cycle 3 Day 1 and Cycle 6 Day 1 or disease progression ]The proportion of patients who over-express ALP in the CTCs, defined as any over-expression, will be estimated using descriptive statistics at each time point. ALP expression will be concurrently examined in the bone metastatic biopsies of men as well, if evaluable tissue is available.
- Change in biomarkers of epithelial plasticity and osteomimicry expressed in the bone metastases of men with bone metastatic CRPC [ Time Frame: At time of optional biopsy, pre- and post-treatment with Radium-223. Post-treatment biopsies will be approximately 10 and 22 weeks after first treatment. ]Summary statistics of other biomarkers involved in epithelial plasticity and osteomimicry in the tumor tissue of men with bone metastatic CRPC including expression of ALP, PSA, CK, O-cadherin, N-cadherin, vimentin, TWIST, SNAIL, beta-catenin, ZEB1, androgen receptor (AR), AR variants (ARv) and γ-H2AX will be completed.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02204943
|United States, North Carolina|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|Principal Investigator:||Andrew Armstrong, MD||Duke University|