This phase II trial studies how well stereotactic ablative radiation therapy (SABR) with or without radium-223 works in treating patients with prostate cancer that has spread to the bone (bone metastases) or soft tissue (soft tissue metastases). SABR uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Radioactive drugs, such as radium-223, may carry radiation directly to tumor cells and not harm normal cells. Giving SABR together with radium-223 may work better in treating patients with prostate cancer compared to SABR alone.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT04037358.
PRIMARY OBJECTIVE:
I. To determine the progression-free survival of men who have oligometastatic prostate cancer with at least one bone metastasis with stereotactic ablative radiation therapy (SABR) versus SABR + radium Ra 223 dichloride (radium 223).
SECONDARY OBJECTIVES:
I. To assess the toxicity of SABR + radium-223 in patients with oligometastatic disease.
II. To determine local control at 12-months after SABR + radium-223 in patients with oligometastatic disease.
III. To assess time to locoregional progression, time to distant progression, time to new metastasis and duration of response after randomization to SABR versus SABR + radium-223.
IV. To assess androgen deprivation therapy (ADT)-free survival after randomization to SABR versus SABR + radium-223.
V. To assess quality of life following completion of SABR + radium-223.
CORRELATIVE OBJECTIVES:
I. To enumerate circulating tumor cells (CTC) using EPIC high definition (HD)-CTC platforms at baseline and 6 months from randomization.
II. To enumerate circulating tumor deoxyribonucleic acid (DNA) (ctDNA) using cancer personalized profiling by deep sequencing (CAPP-Seq) at baseline, months 3, 6 and 12 from randomization for SABR versus SABR + radium-223 arms.
III. To quantitatively sequence T-cell receptor (TCR) repertoires using peripheral blood monocytes and the ImmunoSEQ platform at baseline and 3 months from randomization.
IV. To evaluate immunophenotypes by running peripheral blood mononuclear cells (PBMCs) through a Cytek aurora machine, which allows for simultaneous detection of up to 25 markers.
IVa. To evaluate metabolic fitness of the total PBMCs using the mitochondrial stress test on the seahorse analyzer.
IVb. To determine the relative capacity of peripheral T cells to metabolically respond to T cell receptor stimulation through activation of CD3 and CD28 by running functional assays on PBMCs.
V. To determine frequency of germline DNA repair mutations in the oligometastatic state.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Within 3 weeks of the initial treatment planning imaging study, patients undergo SABR over 1-5 fractions.
ARM II: Within 3 weeks of the initial treatment planning imaging study, patients undergo SABR over 1-5 fractions. Within 4 weeks of randomization, patients also receive radium-223 intravenously (IV) over 1 minute every 4 weeks for a total of 6 doses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3-6 months for up to 24 months.
Lead OrganizationJohns Hopkins University/Sidney Kimmel Cancer Center
Principal InvestigatorAna Ponce Kiess
