PRIMARY OBJECTIVE:
I. To determine if the combination of radium-23 dichloride (radium Ra 223 dichloride) and
paclitaxel improves progression-free survival (PFS) compared to paclitaxel alone.
SECONDARY OBJECTIVES:
I. To determine the time to the first symptomatic skeletal event (SSE) (defined as 1st use of
radiation therapy to relieve skeletal symptoms, new symptomatic pathologic vertebral or
non-vertebral bone fractures, spinal cord compression, or tumor-related orthopedic surgical
intervention).
II. To measure the objective response rate (ORR). III. To determine the safety of radium-223
dichloride with paclitaxel. IV. To measure overall survival (OS).
EXPLORATORY OBJECTIVES:
I. To perform molecular profiling assays on malignant and normal tissues, including, but not
limited to, whole exome sequencing (WES) and messenger ribonucleic acid (RNA) sequencing
(RNAseq), in order to:
Ia. Investigate if molecular alterations in deoxyribonucleic acid (DNA) repair genes are
associated with response to radium-223 dichloride, and; Ib. Investigate if loss of
heterozygosity in triple negative tumors is associated with response to radium-223
dichloride.
II. To contribute genetic analysis data from de-identified biospecimens to Genomic Data
Commons (GDC), a well annotated cancer molecular and clinical data repository, for current
and future research; specimens will be annotated with key clinical data, including
presentation, diagnosis, staging, summary treatment, and if possible, outcome.
III. To correlate change in level of total alkaline phosphatase, bone-specific alkaline
phosphatase, and serum osteocalcin to response to radium-223 dichloride therapy.
IV. To examine the radium-223 dichloride bio-distribution and absorbed dose in each bone
metastatic lesions as well as elsewhere in the body including critical organs using
dosimetry.
V. To bank formalin-fixed, paraffin-embedded (FFPE) tissue, blood, and nucleic acids obtained
from patients at the Experimental Therapeutics Clinical Trials Network (ETCTN) Biorepository
at Nationwide Children's Hospital.
VI. To explore the symptomatic adverse events (AE) for tolerability of each treatment arm.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive paclitaxel intravenously (IV) over 1 hour on days 1, 8, and 15 and
radium Ra 223 dichloride IV over 1 minute on day 1 of each cycle. Treatment with radium Ra
223 dichloride repeats every 28 days for 6 cycles and treatment with paclitaxel repeats every
28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo
computed tomography (CT) scan, bone scan and/or magnetic resonance imaging (MRI), as well as
collection of blood samples throughout trial. Patients may optionally undergo single photon
emission computed tomography (SPECT) on trial.
ARM II: Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15 of each cycle. Cycles
repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients
also undergo CT scan, bone scan, and/or MRI, as well as collection of blood samples
throughout trial. Patients may optionally undergo SPECT on trial.
After completion of study treatment, patients are followed up at 30 days, then every 3 months
for 2 years.