Trial Outcomes & Findings for A Biomarker Study of Standard-of-care Radium-223 Chloride for Metastatic Castration-resistant Prostate Cancer (NCT NCT02346526)

Last Updated: 2022-09-29

Results Overview

Automated bone scan index (aBSI) is an imaging prognostic biomarker used to quantitatively assess effect of therapy. aBSI expresses the tumor burden in bone as a percent of the total skeletal mass. An aBSI value of 1.0 indicates the tumor(s) to be present in 1% of the entire skeleton (arms and legs included).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

22 participants

Primary outcome timeframe

Baseline to 2 Months

Results posted on

2022-09-29

Participant Flow

Participant milestones

Participant milestones
Measure	Radium-223 Dichloride After the screening procedures confirm that a patient is eligible to participate in the research study. Ra-223- Each treatment cycle lasts 4 weeks during which the patient receives Ra-223 by intravenous infusion on day 1 only. Treatments are given every 4 weeks for a total of 6 treatments. These treatments are designed to be entirely standard. Extra testing during and after that six month period will be added to standard testing and monitoring. * Blood Tests * CT scan * Bone scan * FACBC PET/MRI in a subset of participants Blood Tests: Blood will be drawn for standard and nonstandard testing on day one, day 4, and weeks 5, 9, 13, 17, 21, 25, 37, and 93. CT scan: Standard CT scans will be carried out prior to treatment, week 9, and week 25. FACBC PET/MRI in a subset of participants: Approximately half of the study patients (n=10) will undergo experimental FACBC PET/MRI testing at 2 time points each: (1) prior to therapy, and (2) week 9. Radium-223 dichloride: Ra-223- Each treatment cycle lasts 4 weeks during which the patient receives Ra-223 at a dose of 50 kBq/kg body weight by intravenous infusion on day 1 only. Treatments are given every 4 weeks for a total of 6 treatments. bone scan: Standard bone scans will be carried out prior to treatment, week 9, and week 25.
Overall Study STARTED	22
Overall Study COMPLETED	22
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Biomarker Study of Standard-of-care Radium-223 Chloride for Metastatic Castration-resistant Prostate Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Radium-223 Dichloride n=22 Participants After the screening procedures confirm that a patient is eligible to participate in the research study. Ra-223- Each treatment cycle lasts 4 weeks during which the patient receives Ra-223 by intravenous infusion on day 1 only. Treatments are given every 4 weeks for a total of 6 treatments. These treatments are designed to be entirely standard. Extra testing during and after that six month period will be added to standard testing and monitoring. * Blood Tests * CT scan * Bone scan * FACBC PET/MRI in a subset of participants Blood Tests: Blood will be drawn for standard and nonstandard testing on day one, day 4, and weeks 5, 9, 13, 17, 21, 25, 37, and 93. CT scan: Standard CT scans will be carried out prior to treatment, week 9, and week 25. FACBC PET/MRI in a subset of participants: Approximately half of the study patients (n=10) will undergo experimental FACBC PET/MRI testing at 2 time points each: (1) prior to therapy, and (2) week 9. Radium-223 dichloride: Ra-223- Each treatment cycle lasts 4 weeks during which the patient receives Ra-223 at a dose of 50 kBq/kg body weight by intravenous infusion on day 1 only. Treatments are given every 4 weeks for a total of 6 treatments. bone scan: Standard bone scans will be carried out prior to treatment, week 9, and week 25.
Age, Customized Age	71 years n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	22 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	18 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants
Current Use of Bisphosphonates Yes	4 Participants n=5 Participants
Current Use of Bisphosphonates No	18 Participants n=5 Participants
Any Prior Use of Docetaxel Yes	5 Participants n=5 Participants
Any Prior Use of Docetaxel No	17 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Score 0	10 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Score 1	12 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Score greater than or equal to 2	0 Participants n=5 Participants
Extent of disease Less than 6 metastases	8 Participants n=5 Participants
Extent of disease 6 to 20 metastases	7 Participants n=5 Participants
Extent of disease Greater than 20 metastases	7 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to 2 Months

Outcome measures

Outcome measures
Measure	Radium-223 Dichloride n=22 Participants After the screening procedures confirm that a patient is eligible to participate in the research study. Ra-223- Each treatment cycle lasts 4 weeks during which the patient receives Ra-223 by intravenous infusion on day 1 only. Treatments are given every 4 weeks for a total of 6 treatments. These treatments are designed to be entirely standard. Extra testing during and after that six month period will be added to standard testing and monitoring. * Blood Tests * CT scan * Bone scan * FACBC PET/MRI in a subset of participants Blood Tests: Blood will be drawn for standard and nonstandard testing on day one, day 4, and weeks 5, 9, 13, 17, 21, 25, 37, and 93. CT scan: Standard CT scans will be carried out prior to treatment, week 9, and week 25. FACBC PET/MRI in a subset of participants: Approximately half of the study patients (n=10) will undergo experimental FACBC PET/MRI testing at 2 time points each: (1) prior to therapy, and (2) week 9. Radium-223 dichloride: Ra-223- Each treatment cycle lasts 4 weeks during which the patient receives Ra-223 at a dose of 50 kBq/kg body weight by intravenous infusion on day 1 only. Treatments are given every 4 weeks for a total of 6 treatments. bone scan: Standard bone scans will be carried out prior to treatment, week 9, and week 25.	Radium-223 Dichloride / Deceased at 18 Months After the screening procedures confirm that a patient is eligible to participate in the research study. Ra-223- Each treatment cycle lasts 4 weeks during which the patient receives Ra-223 by intravenous infusion on day 1 only. Treatments are given every 4 weeks for a total of 6 treatments. These treatments are designed to be entirely standard. Extra testing during and after that six month period will be added to standard testing and monitoring. * Blood Tests * CT scan * Bone scan * FACBC PET/MRI in a subset of participants Blood Tests: Blood will be drawn for standard and nonstandard testing on day one, day 4, and weeks 5, 9, 13, 17, 21, 25, 37, and 93. CT scan: Standard CT scans will be carried out prior to treatment, week 9, and week 25. FACBC PET/MRI in a subset of participants: Approximately half of the study patients (n=10) will undergo experimental FACBC PET/MRI testing at 2 time points each: (1) prior to therapy, and (2) week 9. Radium-223 dichloride: Ra-223- Each treatment cycle lasts 4 weeks during which the patient receives Ra-223 at a dose of 50 kBq/kg body weight by intravenous infusion on day 1 only. Treatments are given every 4 weeks for a total of 6 treatments. bone scan: Standard bone scans will be carried out prior to treatment, week 9, and week 25.
Bone Scan Index aBSI at Baseline	2.90 percentage of skeletal mass Standard Deviation 3.44	—
Bone Scan Index aBSI at 2 months	3.79 percentage of skeletal mass Standard Deviation 4.28	—

SECONDARY outcome

Timeframe: Baseline and 2 months

Mean change in automated bone scan index (aBSI) at 2 months (i.e. approximately week 9) as assessed by aBSI will be described by 18 month survival status. In other words, decline in aBSI at 2 months on therapy will be evaluated as a predictive biomarker of survival at 18 months.

Outcome measures

Outcome measures
Measure	Radium-223 Dichloride n=12 Participants After the screening procedures confirm that a patient is eligible to participate in the research study. Ra-223- Each treatment cycle lasts 4 weeks during which the patient receives Ra-223 by intravenous infusion on day 1 only. Treatments are given every 4 weeks for a total of 6 treatments. These treatments are designed to be entirely standard. Extra testing during and after that six month period will be added to standard testing and monitoring. * Blood Tests * CT scan * Bone scan * FACBC PET/MRI in a subset of participants Blood Tests: Blood will be drawn for standard and nonstandard testing on day one, day 4, and weeks 5, 9, 13, 17, 21, 25, 37, and 93. CT scan: Standard CT scans will be carried out prior to treatment, week 9, and week 25. FACBC PET/MRI in a subset of participants: Approximately half of the study patients (n=10) will undergo experimental FACBC PET/MRI testing at 2 time points each: (1) prior to therapy, and (2) week 9. Radium-223 dichloride: Ra-223- Each treatment cycle lasts 4 weeks during which the patient receives Ra-223 at a dose of 50 kBq/kg body weight by intravenous infusion on day 1 only. Treatments are given every 4 weeks for a total of 6 treatments. bone scan: Standard bone scans will be carried out prior to treatment, week 9, and week 25.	Radium-223 Dichloride / Deceased at 18 Months n=10 Participants After the screening procedures confirm that a patient is eligible to participate in the research study. Ra-223- Each treatment cycle lasts 4 weeks during which the patient receives Ra-223 by intravenous infusion on day 1 only. Treatments are given every 4 weeks for a total of 6 treatments. These treatments are designed to be entirely standard. Extra testing during and after that six month period will be added to standard testing and monitoring. * Blood Tests * CT scan * Bone scan * FACBC PET/MRI in a subset of participants Blood Tests: Blood will be drawn for standard and nonstandard testing on day one, day 4, and weeks 5, 9, 13, 17, 21, 25, 37, and 93. CT scan: Standard CT scans will be carried out prior to treatment, week 9, and week 25. FACBC PET/MRI in a subset of participants: Approximately half of the study patients (n=10) will undergo experimental FACBC PET/MRI testing at 2 time points each: (1) prior to therapy, and (2) week 9. Radium-223 dichloride: Ra-223- Each treatment cycle lasts 4 weeks during which the patient receives Ra-223 at a dose of 50 kBq/kg body weight by intravenous infusion on day 1 only. Treatments are given every 4 weeks for a total of 6 treatments. bone scan: Standard bone scans will be carried out prior to treatment, week 9, and week 25.
Percentage of Skeletal Mass Occupied by a Lesion, Stratified by 18 Month Survival Status aBSI at Baseline	1.55 percentage of skeletal mass Standard Deviation 1.86	4.38 percentage of skeletal mass Standard Deviation 4.25
Percentage of Skeletal Mass Occupied by a Lesion, Stratified by 18 Month Survival Status aBSI at 2 months	2.24 percentage of skeletal mass Standard Deviation 2.59	6.44 percentage of skeletal mass Standard Deviation 5.60

SECONDARY outcome

Timeframe: Baseline/Day 1, Day 30, Day 60

The presence of circulating tumor cells (CTCs) in the peripheral blood, will be assessed by by the FDA-approved assay CELLSEARCH® CTC Test, is associated with decreased progression-free survival and decreased overall survival in patients treated for metastatic prostate cancer.

Outcome measures

Outcome measures
Measure	Radium-223 Dichloride n=12 Participants After the screening procedures confirm that a patient is eligible to participate in the research study. Ra-223- Each treatment cycle lasts 4 weeks during which the patient receives Ra-223 by intravenous infusion on day 1 only. Treatments are given every 4 weeks for a total of 6 treatments. These treatments are designed to be entirely standard. Extra testing during and after that six month period will be added to standard testing and monitoring. * Blood Tests * CT scan * Bone scan * FACBC PET/MRI in a subset of participants Blood Tests: Blood will be drawn for standard and nonstandard testing on day one, day 4, and weeks 5, 9, 13, 17, 21, 25, 37, and 93. CT scan: Standard CT scans will be carried out prior to treatment, week 9, and week 25. FACBC PET/MRI in a subset of participants: Approximately half of the study patients (n=10) will undergo experimental FACBC PET/MRI testing at 2 time points each: (1) prior to therapy, and (2) week 9. Radium-223 dichloride: Ra-223- Each treatment cycle lasts 4 weeks during which the patient receives Ra-223 at a dose of 50 kBq/kg body weight by intravenous infusion on day 1 only. Treatments are given every 4 weeks for a total of 6 treatments. bone scan: Standard bone scans will be carried out prior to treatment, week 9, and week 25.	Radium-223 Dichloride / Deceased at 18 Months n=10 Participants After the screening procedures confirm that a patient is eligible to participate in the research study. Ra-223- Each treatment cycle lasts 4 weeks during which the patient receives Ra-223 by intravenous infusion on day 1 only. Treatments are given every 4 weeks for a total of 6 treatments. These treatments are designed to be entirely standard. Extra testing during and after that six month period will be added to standard testing and monitoring. * Blood Tests * CT scan * Bone scan * FACBC PET/MRI in a subset of participants Blood Tests: Blood will be drawn for standard and nonstandard testing on day one, day 4, and weeks 5, 9, 13, 17, 21, 25, 37, and 93. CT scan: Standard CT scans will be carried out prior to treatment, week 9, and week 25. FACBC PET/MRI in a subset of participants: Approximately half of the study patients (n=10) will undergo experimental FACBC PET/MRI testing at 2 time points each: (1) prior to therapy, and (2) week 9. Radium-223 dichloride: Ra-223- Each treatment cycle lasts 4 weeks during which the patient receives Ra-223 at a dose of 50 kBq/kg body weight by intravenous infusion on day 1 only. Treatments are given every 4 weeks for a total of 6 treatments. bone scan: Standard bone scans will be carried out prior to treatment, week 9, and week 25.
Circulating Tumor Cell (CTC) Number Day 60	11.71 circulating tumor cells Standard Deviation 21.51	26.86 circulating tumor cells Standard Deviation 28.05
Circulating Tumor Cell (CTC) Number Baseline/Day 1	14.70 circulating tumor cells Standard Deviation 29.64	18.44 circulating tumor cells Standard Deviation 25.36
Circulating Tumor Cell (CTC) Number Day 30	24.71 circulating tumor cells Standard Deviation 61.00	15.57 circulating tumor cells Standard Deviation 12.37

SECONDARY outcome

Timeframe: Baseline/Day 1, Day 30, Day 60

Bone turnover markers (i.e., serum bone specific alkaline phosphatase and N-telopeptide) and plasma biomarkers of inflammation and angiogenesis will be assessed serially. Our analyses of circulating biomarkers of the tumor microenvironment were more limited than originally planned due to a freezer malfunction that compromised our frozen samples that had been saved for later batched analyses. The reported values within the table below reflect CTCm score which is a previously described analysis that uses droplet digital PCR to assess gene expression from circulating tumor cells (CTCs) isolated using the microfluidic CTC-iChip. CTCm score, by published convention, does not have units and does not have a normal range. In the present study, the normalized CTCm score was calculated as described previously using weighting coefficients. It is considered better to have a lower CTCm score. The table contains \[mean (standard deviation)\] of CTCm score for each group at the specified timepo

Outcome measures

Outcome measures
Measure	Radium-223 Dichloride n=12 Participants After the screening procedures confirm that a patient is eligible to participate in the research study. Ra-223- Each treatment cycle lasts 4 weeks during which the patient receives Ra-223 by intravenous infusion on day 1 only. Treatments are given every 4 weeks for a total of 6 treatments. These treatments are designed to be entirely standard. Extra testing during and after that six month period will be added to standard testing and monitoring. * Blood Tests * CT scan * Bone scan * FACBC PET/MRI in a subset of participants Blood Tests: Blood will be drawn for standard and nonstandard testing on day one, day 4, and weeks 5, 9, 13, 17, 21, 25, 37, and 93. CT scan: Standard CT scans will be carried out prior to treatment, week 9, and week 25. FACBC PET/MRI in a subset of participants: Approximately half of the study patients (n=10) will undergo experimental FACBC PET/MRI testing at 2 time points each: (1) prior to therapy, and (2) week 9. Radium-223 dichloride: Ra-223- Each treatment cycle lasts 4 weeks during which the patient receives Ra-223 at a dose of 50 kBq/kg body weight by intravenous infusion on day 1 only. Treatments are given every 4 weeks for a total of 6 treatments. bone scan: Standard bone scans will be carried out prior to treatment, week 9, and week 25.	Radium-223 Dichloride / Deceased at 18 Months n=10 Participants After the screening procedures confirm that a patient is eligible to participate in the research study. Ra-223- Each treatment cycle lasts 4 weeks during which the patient receives Ra-223 by intravenous infusion on day 1 only. Treatments are given every 4 weeks for a total of 6 treatments. These treatments are designed to be entirely standard. Extra testing during and after that six month period will be added to standard testing and monitoring. * Blood Tests * CT scan * Bone scan * FACBC PET/MRI in a subset of participants Blood Tests: Blood will be drawn for standard and nonstandard testing on day one, day 4, and weeks 5, 9, 13, 17, 21, 25, 37, and 93. CT scan: Standard CT scans will be carried out prior to treatment, week 9, and week 25. FACBC PET/MRI in a subset of participants: Approximately half of the study patients (n=10) will undergo experimental FACBC PET/MRI testing at 2 time points each: (1) prior to therapy, and (2) week 9. Radium-223 dichloride: Ra-223- Each treatment cycle lasts 4 weeks during which the patient receives Ra-223 at a dose of 50 kBq/kg body weight by intravenous infusion on day 1 only. Treatments are given every 4 weeks for a total of 6 treatments. bone scan: Standard bone scans will be carried out prior to treatment, week 9, and week 25.
Circulating Biomarkers of the Tumor Microenvironment Baseline/Day 1	91.11 gene expression score per 7.5mL blood Standard Deviation 201.94	302.40 gene expression score per 7.5mL blood Standard Deviation 762.97
Circulating Biomarkers of the Tumor Microenvironment Day 30	102.25 gene expression score per 7.5mL blood Standard Deviation 248.64	42.21 gene expression score per 7.5mL blood Standard Deviation 57.95
Circulating Biomarkers of the Tumor Microenvironment Day 60	294.52 gene expression score per 7.5mL blood Standard Deviation 493.61	138.29 gene expression score per 7.5mL blood Standard Deviation 138.02

SECONDARY outcome

Timeframe: Baseline through study completion, up to approximately 5 years

Population: Only 20 out of 22 participants were analyzed due to participant non-compliance.

Pain and narcotic analgesic use was assessed by the 4-item Brief Pain Inventory (BPI). This instrument contains 4 items, with each item reported on a scale of 0-10, meaning that total possible range is 0-40. For each question's 0-10 response scale, 0 meant no pain/interference and 10 meant worst pain imaginable/complete interference. Overall survival (OS) was defined as the interval between the start of therapy and the date of death or censor. For the analysis presented in the table, the algorithm of Contal-O'Quigley was applied to the data using leave-one-out jack-knife resampling to determine the optimal division points according to pain score on 4-item BPI at baseline. Each iteration of the algorithm produced an estimate of the "best" division point based on the data. With this method, optimal cut-point for this cohort was baseline total BPI score \< 8 vs ≥8. Median survival for each sub-group is reported as months (with range in parentheses).

Outcome measures

Outcome measures
Measure	Radium-223 Dichloride n=6 Participants After the screening procedures confirm that a patient is eligible to participate in the research study. Ra-223- Each treatment cycle lasts 4 weeks during which the patient receives Ra-223 by intravenous infusion on day 1 only. Treatments are given every 4 weeks for a total of 6 treatments. These treatments are designed to be entirely standard. Extra testing during and after that six month period will be added to standard testing and monitoring. * Blood Tests * CT scan * Bone scan * FACBC PET/MRI in a subset of participants Blood Tests: Blood will be drawn for standard and nonstandard testing on day one, day 4, and weeks 5, 9, 13, 17, 21, 25, 37, and 93. CT scan: Standard CT scans will be carried out prior to treatment, week 9, and week 25. FACBC PET/MRI in a subset of participants: Approximately half of the study patients (n=10) will undergo experimental FACBC PET/MRI testing at 2 time points each: (1) prior to therapy, and (2) week 9. Radium-223 dichloride: Ra-223- Each treatment cycle lasts 4 weeks during which the patient receives Ra-223 at a dose of 50 kBq/kg body weight by intravenous infusion on day 1 only. Treatments are given every 4 weeks for a total of 6 treatments. bone scan: Standard bone scans will be carried out prior to treatment, week 9, and week 25.	Radium-223 Dichloride / Deceased at 18 Months n=14 Participants After the screening procedures confirm that a patient is eligible to participate in the research study. Ra-223- Each treatment cycle lasts 4 weeks during which the patient receives Ra-223 by intravenous infusion on day 1 only. Treatments are given every 4 weeks for a total of 6 treatments. These treatments are designed to be entirely standard. Extra testing during and after that six month period will be added to standard testing and monitoring. * Blood Tests * CT scan * Bone scan * FACBC PET/MRI in a subset of participants Blood Tests: Blood will be drawn for standard and nonstandard testing on day one, day 4, and weeks 5, 9, 13, 17, 21, 25, 37, and 93. CT scan: Standard CT scans will be carried out prior to treatment, week 9, and week 25. FACBC PET/MRI in a subset of participants: Approximately half of the study patients (n=10) will undergo experimental FACBC PET/MRI testing at 2 time points each: (1) prior to therapy, and (2) week 9. Radium-223 dichloride: Ra-223- Each treatment cycle lasts 4 weeks during which the patient receives Ra-223 at a dose of 50 kBq/kg body weight by intravenous infusion on day 1 only. Treatments are given every 4 weeks for a total of 6 treatments. bone scan: Standard bone scans will be carried out prior to treatment, week 9, and week 25.
Baseline Pain Score Evaluation as a Predictor of Survival	9.35 months Interval 4.1 to 17.5	33.85 months Interval 2.1 to 49.6

SECONDARY outcome

Timeframe: Baseline through study completion, up to approximately 5 years.

Population: Only 21 out of 22 participants were analyzed due to participant non-compliance.

Baseline Global Health Score was reported by participants on a scale of 0 ("The worst health you can imagine") to 100 ("The best health you can imagine"). Overall survival (OS) was defined as the interval between the start of therapy and the date of death or censor, expressed here in months. For the analysis presented in the table, the algorithm of Contal-O'Quigley was applied to the data using leave-one-out jack- knife resampling to determine the optimal division points according to Global Health Score at baseline. Each iteration of the algorithm produced an estimate of the "best" division point based on the data. With this method, optimal cut-point for this cohort was baseline Global Health Score ≥95 or \<95. Median survival for each sub-group is reported as months (with range in parentheses).

Outcome measures

Outcome measures
Measure	Radium-223 Dichloride n=7 Participants After the screening procedures confirm that a patient is eligible to participate in the research study. Ra-223- Each treatment cycle lasts 4 weeks during which the patient receives Ra-223 by intravenous infusion on day 1 only. Treatments are given every 4 weeks for a total of 6 treatments. These treatments are designed to be entirely standard. Extra testing during and after that six month period will be added to standard testing and monitoring. * Blood Tests * CT scan * Bone scan * FACBC PET/MRI in a subset of participants Blood Tests: Blood will be drawn for standard and nonstandard testing on day one, day 4, and weeks 5, 9, 13, 17, 21, 25, 37, and 93. CT scan: Standard CT scans will be carried out prior to treatment, week 9, and week 25. FACBC PET/MRI in a subset of participants: Approximately half of the study patients (n=10) will undergo experimental FACBC PET/MRI testing at 2 time points each: (1) prior to therapy, and (2) week 9. Radium-223 dichloride: Ra-223- Each treatment cycle lasts 4 weeks during which the patient receives Ra-223 at a dose of 50 kBq/kg body weight by intravenous infusion on day 1 only. Treatments are given every 4 weeks for a total of 6 treatments. bone scan: Standard bone scans will be carried out prior to treatment, week 9, and week 25.	Radium-223 Dichloride / Deceased at 18 Months n=14 Participants After the screening procedures confirm that a patient is eligible to participate in the research study. Ra-223- Each treatment cycle lasts 4 weeks during which the patient receives Ra-223 by intravenous infusion on day 1 only. Treatments are given every 4 weeks for a total of 6 treatments. These treatments are designed to be entirely standard. Extra testing during and after that six month period will be added to standard testing and monitoring. * Blood Tests * CT scan * Bone scan * FACBC PET/MRI in a subset of participants Blood Tests: Blood will be drawn for standard and nonstandard testing on day one, day 4, and weeks 5, 9, 13, 17, 21, 25, 37, and 93. CT scan: Standard CT scans will be carried out prior to treatment, week 9, and week 25. FACBC PET/MRI in a subset of participants: Approximately half of the study patients (n=10) will undergo experimental FACBC PET/MRI testing at 2 time points each: (1) prior to therapy, and (2) week 9. Radium-223 dichloride: Ra-223- Each treatment cycle lasts 4 weeks during which the patient receives Ra-223 at a dose of 50 kBq/kg body weight by intravenous infusion on day 1 only. Treatments are given every 4 weeks for a total of 6 treatments. bone scan: Standard bone scans will be carried out prior to treatment, week 9, and week 25.
Baseline Global Health Score Evaluation as a Predictor of Survival	39.90 months Interval 19.3 to 49.6	12.85 months Interval 2.1 to 33.2

Adverse Events

Radium-223 Dichloride

Serious events: 0 serious events

Other events: 8 other events

Deaths: 18 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Radium-223 Dichloride n=22 participants at risk Ra-223: Each treatment cycle lasted 4 weeks during which the patient received Ra-223 by intravenous infusion on day 1 only. Treatments were given every 4 weeks for a total of 6 treatments. These treatments were designed to be entirely standard. Extra testing during and after that six month period was added to standard testing and monitoring (blood tests, CT, bone scan, and FACBC (fluciclovine) PET/MRI in a subset of participants). Blood Tests: Blood was drawn for standard and nonstandard testing on day 1, day 4, and weeks 5, 9, 13, 17, 21, 25, 37, and 93. CT scan: Standard CT scans will be carried out prior to treatment, week 9, and week 25. FACBC (fluciclovine) PET/MRI in a subset of participants: Approximately half of the study patients (n=10) underwent experimental FACBC (fluciclovine) PET/MRI testing at 2 time points each: (1) prior to therapy, and (2) week 9. We did not separate the PET/MRI and non-PET/MRI groups within this adverse event reporting because therapy was identical regardless of whether that imaging was done. The PET and MRI used per this protocol were both clinically available tests (i.e., not experimental). Radium-223 dichloride: Each treatment cycle lasted 4 weeks during which the patient received Ra-223 at a dose of 50 kBq/kg body weight by intravenous infusion on day 1 only. Treatments were given every 4 weeks for a total of 6 treatments. Bone scan: Standard bone scans were carried out prior to treatment, week 9, and week 25.
Psychiatric disorders Depression	4.5% 1/22 • Number of events 1 • through study completion, up to approximately 5 years
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify	4.5% 1/22 • Number of events 1 • through study completion, up to approximately 5 years
Skin and subcutaneous tissue disorders Dry skin	4.5% 1/22 • Number of events 1 • through study completion, up to approximately 5 years
Metabolism and nutrition disorders Anorexia	4.5% 1/22 • Number of events 1 • through study completion, up to approximately 5 years
Nervous system disorders Dizziness	4.5% 1/22 • Number of events 1 • through study completion, up to approximately 5 years
General disorders General disorders and administration site conditions - Other, specify	4.5% 1/22 • Number of events 1 • through study completion, up to approximately 5 years
Renal and urinary disorders Urinary incontinence	4.5% 1/22 • Number of events 1 • through study completion, up to approximately 5 years
Musculoskeletal and connective tissue disorders Back pain	4.5% 1/22 • Number of events 1 • through study completion, up to approximately 5 years
Musculoskeletal and connective tissue disorders Pain in extremity	9.1% 2/22 • Number of events 2 • through study completion, up to approximately 5 years
Musculoskeletal and connective tissue disorders Arthritis	4.5% 1/22 • Number of events 1 • through study completion, up to approximately 5 years
General disorders Pain	4.5% 1/22 • Number of events 1 • through study completion, up to approximately 5 years
Nervous system disorders Headache	4.5% 1/22 • Number of events 1 • through study completion, up to approximately 5 years
Nervous system disorders Paresthesia	4.5% 1/22 • Number of events 1 • through study completion, up to approximately 5 years
Blood and lymphatic system disorders Anemia	4.5% 1/22 • Number of events 1 • through study completion, up to approximately 5 years
General disorders Edema limbs	4.5% 1/22 • Number of events 1 • through study completion, up to approximately 5 years
Injury, poisoning and procedural complications Spinal fracture	4.5% 1/22 • Number of events 1 • through study completion, up to approximately 5 years
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorders - other, specify	4.5% 1/22 • Number of events 1 • through study completion, up to approximately 5 years

Additional Information

Philip Saylor, MD

Massachusetts General Hospital

Phone: 617-724-5197

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place