Trial Outcomes & Findings for Open Label Phase Two Trial of Radium Ra 223 Dichloride With Concurrent Administration of Abiraterone Acetate Plus Prednisone in Symptomatic Castration-Resistant (Hormone-Refractory) Prostate Cancer Subjects With Bone Metastasis (NCT NCT02097303)
NCT ID: NCT02097303
Last Updated: 2018-02-01
Results Overview
Following Quality of Life questionnaires were given at each visit: FACT-P assesses symptoms/problems related to prostate carcinoma and its treatment. It is a combination of the FACT- General + the PCS (Range 1-156, higher scores better). The FACT-General (FACT-G) is a 28 item QOL measure that provides a total score as well as subscale scores: Physical (0-28), Functional (0-28), Social (0-28), Emotional (0-24) Well-being, and Satisfaction with Treatment was not assessed for this study (The total range was between 1-108, higher scores better) FACT-TOI is derived from the sum of the Physical Well-Being, Functional Well-Being, and Prostate Cancer subscale scores; a sensitive measure of patient-reported health (Range 1-104, higher scores better) PCS is a 12-item prostate cancer subscale that asks about symptoms and problems specific to prostate cancer (Range 0-48, higher scores better).
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
36 participants
Primary outcome timeframe
Subjects were evaluated at the screening visit, monthly during the study, and 30 days after the last dose of Radium Ra 223 dichloride, which will be approximately 32 weeks after the screening visit of evaluable subjects.
Results posted on
2018-02-01
Participant Flow
Participant milestones
| Measure |
Radium 223 With Concomitant Abiraterone Acetate and Prednisone
Name of active ingredient Radium Ra 223 dichloride Dose 50 kBq/kg body weight Route of Administration Intravenous Duration of Treatment One injection every 4 weeks X 6 injections maximum.
Name of active ingredient Abiraterone Acetate plus Prednisone Dose 1000 mg/day and 5 mg BID Route of Administration Oral Duration of Treatment 26 weeks minimum duration. There is no maximum duration.
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|---|---|
|
Overall Study
STARTED
|
36
|
|
Overall Study
COMPLETED
|
31
|
|
Overall Study
NOT COMPLETED
|
5
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Open Label Phase Two Trial of Radium Ra 223 Dichloride With Concurrent Administration of Abiraterone Acetate Plus Prednisone in Symptomatic Castration-Resistant (Hormone-Refractory) Prostate Cancer Subjects With Bone Metastasis
Baseline characteristics by cohort
| Measure |
Radium 223 With Concomitant Abiraterone Acetate and Prednisone
n=36 Participants
Name of active ingredient Radium Ra 223 dichloride Dose 50 kBq/kg body weight Route of Administration Intravenous Duration of Treatment One injection every 4 weeks X 6 injections maximum.
Name of active ingredient Abiraterone Acetate plus Prednisone Dose 1000 mg/day and 5 mg BID Route of Administration Oral Duration of Treatment 26 weeks minimum duration. There is no maximum duration.
|
|---|---|
|
Age, Continuous
|
75 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
36 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Non-Hispanic or Latino
|
36 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
28 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
African American
|
8 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
36 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Subjects were evaluated at the screening visit, monthly during the study, and 30 days after the last dose of Radium Ra 223 dichloride, which will be approximately 32 weeks after the screening visit of evaluable subjects.Population: Improvement at the EOT visit was defined as increase from baseline of \>= 10 points for FACT-P Total Scale. \>9 points for FACT-G Total and FACT-TOI scales, and \>=3 points for the remaining scales.
Following Quality of Life questionnaires were given at each visit: FACT-P assesses symptoms/problems related to prostate carcinoma and its treatment. It is a combination of the FACT- General + the PCS (Range 1-156, higher scores better). The FACT-General (FACT-G) is a 28 item QOL measure that provides a total score as well as subscale scores: Physical (0-28), Functional (0-28), Social (0-28), Emotional (0-24) Well-being, and Satisfaction with Treatment was not assessed for this study (The total range was between 1-108, higher scores better) FACT-TOI is derived from the sum of the Physical Well-Being, Functional Well-Being, and Prostate Cancer subscale scores; a sensitive measure of patient-reported health (Range 1-104, higher scores better) PCS is a 12-item prostate cancer subscale that asks about symptoms and problems specific to prostate cancer (Range 0-48, higher scores better).
Outcome measures
| Measure |
Radium 223 With Concomitant Abiraterone Acetate and Prednisone
n=31 Participants
Name of active ingredient Radium Ra 223 dichloride Dose 50 kBq/kg body weight Route of Administration Intravenous Duration of Treatment One injection every 4 weeks X 6 injections maximum.
Name of active ingredient Abiraterone Acetate plus Prednisone Dose 1000 mg/day and 5 mg BID Route of Administration Oral Duration of Treatment 26 weeks minimum duration. There is no maximum duration.
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|---|---|
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Number and Percentage of Participants With Clinically Meaningful Improvement (Between Baseline and End of Treatment) in Quality-of-Life Determined by the Minimum Increase From Baseline in Scores as Per the QOL CMI Criteria
FACT-P Total Scale
|
20 Participants
|
|
Number and Percentage of Participants With Clinically Meaningful Improvement (Between Baseline and End of Treatment) in Quality-of-Life Determined by the Minimum Increase From Baseline in Scores as Per the QOL CMI Criteria
FACT-G Total Scale
|
18 Participants
|
|
Number and Percentage of Participants With Clinically Meaningful Improvement (Between Baseline and End of Treatment) in Quality-of-Life Determined by the Minimum Increase From Baseline in Scores as Per the QOL CMI Criteria
Treatment Outcome Index (FACT-TOI)
|
18 Participants
|
|
Number and Percentage of Participants With Clinically Meaningful Improvement (Between Baseline and End of Treatment) in Quality-of-Life Determined by the Minimum Increase From Baseline in Scores as Per the QOL CMI Criteria
Prostate Cancer Subscale (PCS)
|
25 Participants
|
|
Number and Percentage of Participants With Clinically Meaningful Improvement (Between Baseline and End of Treatment) in Quality-of-Life Determined by the Minimum Increase From Baseline in Scores as Per the QOL CMI Criteria
Physical Well-being
|
19 Participants
|
|
Number and Percentage of Participants With Clinically Meaningful Improvement (Between Baseline and End of Treatment) in Quality-of-Life Determined by the Minimum Increase From Baseline in Scores as Per the QOL CMI Criteria
Functional Well-being
|
17 Participants
|
|
Number and Percentage of Participants With Clinically Meaningful Improvement (Between Baseline and End of Treatment) in Quality-of-Life Determined by the Minimum Increase From Baseline in Scores as Per the QOL CMI Criteria
Emotional Well-being
|
18 Participants
|
|
Number and Percentage of Participants With Clinically Meaningful Improvement (Between Baseline and End of Treatment) in Quality-of-Life Determined by the Minimum Increase From Baseline in Scores as Per the QOL CMI Criteria
Social Well-being
|
15 Participants
|
PRIMARY outcome
Timeframe: Subjects were evaluated at the screening visit, monthly during the study, and 30 days after the last dose of Radium Ra 223 dichloride, which will be approximately 32 weeks after the screening visit of evaluable subjects.Improvement in Bone Pain was assessed using the Bone Pain Inventory (BPI) 1. Pain Severity: Pain severity is the composite of scores of worst pain, least pain, average pain, and pain now. CMI criteria: Decrease \>30% at two consecutive visits in Pain Severity Score in 24 hours without an increase in analgesic use. 2. Pain interference: Pain interference is the composite scores on general activity, mood, walking ability, normal work, relationships with others, sleep and enjoyment of life. CMI criteria: Decrease by 1.25 points or more compared with baseline at two consecutive visits. 3. Transient Pain Flare: Based on the work of Atkinson et al, a transient pain flare was assessed by pain at its worst in 24 hours. CMI criteria: \> 2 points on the BPI-SF Worst Pain scale and subsequent reduction after initiation of Ra-223 and during the first 3 cycles.
Outcome measures
| Measure |
Radium 223 With Concomitant Abiraterone Acetate and Prednisone
n=31 Participants
Name of active ingredient Radium Ra 223 dichloride Dose 50 kBq/kg body weight Route of Administration Intravenous Duration of Treatment One injection every 4 weeks X 6 injections maximum.
Name of active ingredient Abiraterone Acetate plus Prednisone Dose 1000 mg/day and 5 mg BID Route of Administration Oral Duration of Treatment 26 weeks minimum duration. There is no maximum duration.
|
|---|---|
|
Number and Percentage of Participants With Clinically Meaningful Improvement (CMI) in Pain (Between Baseline and End of Treatment)
Pain Severity
|
18 Participants
|
|
Number and Percentage of Participants With Clinically Meaningful Improvement (CMI) in Pain (Between Baseline and End of Treatment)
Pain Interference
|
12 Participants
|
|
Number and Percentage of Participants With Clinically Meaningful Improvement (CMI) in Pain (Between Baseline and End of Treatment)
Transient Pain Flare
|
2 Participants
|
SECONDARY outcome
Timeframe: Subjects were evaluated at the screening visit, monthly during the study, and 30 days after the last dose of Radium Ra 223 dichloride, which will be approximately 32 weeks after the screening visit of evaluable subjects.All adverse events relevant to advanced mCRPC subjects as well as adverse events of interest for both Abiraterone Acetate plus Prednisone and Radium Ra 223 dichloride will be reported.
Outcome measures
| Measure |
Radium 223 With Concomitant Abiraterone Acetate and Prednisone
n=36 Participants
Name of active ingredient Radium Ra 223 dichloride Dose 50 kBq/kg body weight Route of Administration Intravenous Duration of Treatment One injection every 4 weeks X 6 injections maximum.
Name of active ingredient Abiraterone Acetate plus Prednisone Dose 1000 mg/day and 5 mg BID Route of Administration Oral Duration of Treatment 26 weeks minimum duration. There is no maximum duration.
|
|---|---|
|
Safety Data Was Analyzed and Summarized in Subjects Who Receive at Least One Infusion of Radium Ra 223 Dichloride. Number of Adverse Events Are Being Reported.
Overall Adverse Events
|
186 Adverse Events
|
|
Safety Data Was Analyzed and Summarized in Subjects Who Receive at Least One Infusion of Radium Ra 223 Dichloride. Number of Adverse Events Are Being Reported.
Grade I or II Adverse Events
|
179 Adverse Events
|
|
Safety Data Was Analyzed and Summarized in Subjects Who Receive at Least One Infusion of Radium Ra 223 Dichloride. Number of Adverse Events Are Being Reported.
Treatment Related Adverse Events
|
70 Adverse Events
|
SECONDARY outcome
Timeframe: Baseline and End of Treatment (EOT), approximately 32 weeks from Baseline\[Not specified\]
Outcome measures
| Measure |
Radium 223 With Concomitant Abiraterone Acetate and Prednisone
n=31 Participants
Name of active ingredient Radium Ra 223 dichloride Dose 50 kBq/kg body weight Route of Administration Intravenous Duration of Treatment One injection every 4 weeks X 6 injections maximum.
Name of active ingredient Abiraterone Acetate plus Prednisone Dose 1000 mg/day and 5 mg BID Route of Administration Oral Duration of Treatment 26 weeks minimum duration. There is no maximum duration.
|
|---|---|
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Alkaline Phosphatase (ALP) and Prostate Specific Antigen (PSA) Levels Before and After Treatment
ALP (Baseline)
|
261 ng/dL
Standard Deviation 284
|
|
Alkaline Phosphatase (ALP) and Prostate Specific Antigen (PSA) Levels Before and After Treatment
ALP (EOT)
|
110 ng/dL
Standard Deviation 187
|
|
Alkaline Phosphatase (ALP) and Prostate Specific Antigen (PSA) Levels Before and After Treatment
PSA (Baseline)
|
87 ng/dL
Standard Deviation 233
|
|
Alkaline Phosphatase (ALP) and Prostate Specific Antigen (PSA) Levels Before and After Treatment
PSA (EOT)
|
137 ng/dL
Standard Deviation 441
|
SECONDARY outcome
Timeframe: Baseline and End of Treatment (EOT), approximately 32 weeks from Baseline\[Not Specified\]
Outcome measures
| Measure |
Radium 223 With Concomitant Abiraterone Acetate and Prednisone
n=31 Participants
Name of active ingredient Radium Ra 223 dichloride Dose 50 kBq/kg body weight Route of Administration Intravenous Duration of Treatment One injection every 4 weeks X 6 injections maximum.
Name of active ingredient Abiraterone Acetate plus Prednisone Dose 1000 mg/day and 5 mg BID Route of Administration Oral Duration of Treatment 26 weeks minimum duration. There is no maximum duration.
|
|---|---|
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Radiologic Assessment Mean Number of Bone Lesions Before and After the Treatment
Baseline
|
11.6 Lesions
Standard Deviation 2.8
|
|
Radiologic Assessment Mean Number of Bone Lesions Before and After the Treatment
EOT
|
5.6 Lesions
Standard Deviation 2.4
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline and End of Treatment (EOT), approximately 32 weeks from BaselineBone imaging response was assessed at baseline and at EOT visit. Progression was defined as two or more additional lesions in comparison to the baseline.
Outcome measures
| Measure |
Radium 223 With Concomitant Abiraterone Acetate and Prednisone
n=31 Participants
Name of active ingredient Radium Ra 223 dichloride Dose 50 kBq/kg body weight Route of Administration Intravenous Duration of Treatment One injection every 4 weeks X 6 injections maximum.
Name of active ingredient Abiraterone Acetate plus Prednisone Dose 1000 mg/day and 5 mg BID Route of Administration Oral Duration of Treatment 26 weeks minimum duration. There is no maximum duration.
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|---|---|
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Bone Imaging Response (Number of Participants With Progression and Stable Disease)
Progression
|
2 Participants
|
|
Bone Imaging Response (Number of Participants With Progression and Stable Disease)
Stable Disease
|
29 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline and End of Treatment (EOT), approximately 32 weeks from BaselineDetermination of measurable disease progression or response was based on modified RECIST criteria. Reported is the number of participants with either a partial or complete response, and who had radiological extraskeletal progression.
Outcome measures
| Measure |
Radium 223 With Concomitant Abiraterone Acetate and Prednisone
n=31 Participants
Name of active ingredient Radium Ra 223 dichloride Dose 50 kBq/kg body weight Route of Administration Intravenous Duration of Treatment One injection every 4 weeks X 6 injections maximum.
Name of active ingredient Abiraterone Acetate plus Prednisone Dose 1000 mg/day and 5 mg BID Route of Administration Oral Duration of Treatment 26 weeks minimum duration. There is no maximum duration.
|
|---|---|
|
Overall Response Rate
Progression
|
8 Participants
|
|
Overall Response Rate
Partial or complete response
|
4 Participants
|
Adverse Events
Radium 223 With Concomitant Abiraterone Acetate and Prednisone
Serious events: 5 serious events
Other events: 30 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Radium 223 With Concomitant Abiraterone Acetate and Prednisone
n=36 participants at risk
Name of active ingredient Radium Ra 223 dichloride Dose 50 kBq/kg body weight Route of Administration Intravenous Duration of Treatment One injection every 4 weeks X 6 injections maximum.
Name of active ingredient Abiraterone Acetate plus Prednisone Dose 1000 mg/day and 5 mg BID Route of Administration Oral Duration of Treatment 26 weeks minimum duration. There is no maximum duration.
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|---|---|
|
Gastrointestinal disorders
Abdominal Pain
|
2.8%
1/36 • Number of events 1 • Adverse events were collected from enrollment through 6 monthly cycles, and 30 days after the end of treatment, for a total of 7 months.
|
|
Cardiac disorders
Cardiopulmonary Arrest
|
2.8%
1/36 • Number of events 1 • Adverse events were collected from enrollment through 6 monthly cycles, and 30 days after the end of treatment, for a total of 7 months.
|
|
Infections and infestations
Urinary Tract Infection
|
2.8%
1/36 • Number of events 1 • Adverse events were collected from enrollment through 6 monthly cycles, and 30 days after the end of treatment, for a total of 7 months.
|
|
Cardiac disorders
Syncope
|
2.8%
1/36 • Number of events 1 • Adverse events were collected from enrollment through 6 monthly cycles, and 30 days after the end of treatment, for a total of 7 months.
|
|
Gastrointestinal disorders
Small Bowel Obstruction
|
2.8%
1/36 • Number of events 1 • Adverse events were collected from enrollment through 6 monthly cycles, and 30 days after the end of treatment, for a total of 7 months.
|
|
Cardiac disorders
Congestive Heart Failure
|
2.8%
1/36 • Number of events 1 • Adverse events were collected from enrollment through 6 monthly cycles, and 30 days after the end of treatment, for a total of 7 months.
|
Other adverse events
| Measure |
Radium 223 With Concomitant Abiraterone Acetate and Prednisone
n=36 participants at risk
Name of active ingredient Radium Ra 223 dichloride Dose 50 kBq/kg body weight Route of Administration Intravenous Duration of Treatment One injection every 4 weeks X 6 injections maximum.
Name of active ingredient Abiraterone Acetate plus Prednisone Dose 1000 mg/day and 5 mg BID Route of Administration Oral Duration of Treatment 26 weeks minimum duration. There is no maximum duration.
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
13.9%
5/36 • Number of events 9 • Adverse events were collected from enrollment through 6 monthly cycles, and 30 days after the end of treatment, for a total of 7 months.
|
|
Blood and lymphatic system disorders
Leukopenia
|
8.3%
3/36 • Number of events 4 • Adverse events were collected from enrollment through 6 monthly cycles, and 30 days after the end of treatment, for a total of 7 months.
|
|
Blood and lymphatic system disorders
Neutropenia
|
5.6%
2/36 • Number of events 4 • Adverse events were collected from enrollment through 6 monthly cycles, and 30 days after the end of treatment, for a total of 7 months.
|
|
Blood and lymphatic system disorders
Pancytopenia
|
2.8%
1/36 • Number of events 2 • Adverse events were collected from enrollment through 6 monthly cycles, and 30 days after the end of treatment, for a total of 7 months.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
2.8%
1/36 • Number of events 2 • Adverse events were collected from enrollment through 6 monthly cycles, and 30 days after the end of treatment, for a total of 7 months.
|
|
Gastrointestinal disorders
Diarrhea
|
19.4%
7/36 • Number of events 14 • Adverse events were collected from enrollment through 6 monthly cycles, and 30 days after the end of treatment, for a total of 7 months.
|
|
Gastrointestinal disorders
Nausea
|
19.4%
7/36 • Number of events 21 • Adverse events were collected from enrollment through 6 monthly cycles, and 30 days after the end of treatment, for a total of 7 months.
|
|
Gastrointestinal disorders
Stomach Pain
|
5.6%
2/36 • Number of events 4 • Adverse events were collected from enrollment through 6 monthly cycles, and 30 days after the end of treatment, for a total of 7 months.
|
|
Gastrointestinal disorders
Abdominal Pain
|
2.8%
1/36 • Number of events 2 • Adverse events were collected from enrollment through 6 monthly cycles, and 30 days after the end of treatment, for a total of 7 months.
|
|
Gastrointestinal disorders
Decreased Appetitie
|
2.8%
1/36 • Number of events 3 • Adverse events were collected from enrollment through 6 monthly cycles, and 30 days after the end of treatment, for a total of 7 months.
|
|
Gastrointestinal disorders
Dysguesia
|
2.8%
1/36 • Number of events 1 • Adverse events were collected from enrollment through 6 monthly cycles, and 30 days after the end of treatment, for a total of 7 months.
|
|
Blood and lymphatic system disorders
Edema Limbs
|
8.3%
3/36 • Number of events 6 • Adverse events were collected from enrollment through 6 monthly cycles, and 30 days after the end of treatment, for a total of 7 months.
|
|
Endocrine disorders
Fatigue
|
16.7%
6/36 • Number of events 14 • Adverse events were collected from enrollment through 6 monthly cycles, and 30 days after the end of treatment, for a total of 7 months.
|
|
Hepatobiliary disorders
Increased Liver Function Tests
|
2.8%
1/36 • Number of events 3 • Adverse events were collected from enrollment through 6 monthly cycles, and 30 days after the end of treatment, for a total of 7 months.
|
|
Blood and lymphatic system disorders
Decreased Red Blood Count
|
2.8%
1/36 • Number of events 3 • Adverse events were collected from enrollment through 6 monthly cycles, and 30 days after the end of treatment, for a total of 7 months.
|
|
Hepatobiliary disorders
Increased ALT
|
5.6%
2/36 • Number of events 5 • Adverse events were collected from enrollment through 6 monthly cycles, and 30 days after the end of treatment, for a total of 7 months.
|
|
Hepatobiliary disorders
Increased ALP
|
2.8%
1/36 • Number of events 2 • Adverse events were collected from enrollment through 6 monthly cycles, and 30 days after the end of treatment, for a total of 7 months.
|
|
Investigations
Hypocalcemia
|
5.6%
2/36 • Number of events 3 • Adverse events were collected from enrollment through 6 monthly cycles, and 30 days after the end of treatment, for a total of 7 months.
|
|
Investigations
Hyponatremia
|
2.8%
1/36 • Number of events 2 • Adverse events were collected from enrollment through 6 monthly cycles, and 30 days after the end of treatment, for a total of 7 months.
|
|
Investigations
Hypochloremia
|
2.8%
1/36 • Number of events 2 • Adverse events were collected from enrollment through 6 monthly cycles, and 30 days after the end of treatment, for a total of 7 months.
|
|
Musculoskeletal and connective tissue disorders
Bone Pain
|
2.8%
1/36 • Number of events 3 • Adverse events were collected from enrollment through 6 monthly cycles, and 30 days after the end of treatment, for a total of 7 months.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
2.8%
1/36 • Number of events 2 • Adverse events were collected from enrollment through 6 monthly cycles, and 30 days after the end of treatment, for a total of 7 months.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
2.8%
1/36 • Number of events 3 • Adverse events were collected from enrollment through 6 monthly cycles, and 30 days after the end of treatment, for a total of 7 months.
|
|
Ear and labyrinth disorders
Dizziness
|
5.6%
2/36 • Number of events 5 • Adverse events were collected from enrollment through 6 monthly cycles, and 30 days after the end of treatment, for a total of 7 months.
|
|
Ear and labyrinth disorders
Headaches
|
2.8%
1/36 • Number of events 3 • Adverse events were collected from enrollment through 6 monthly cycles, and 30 days after the end of treatment, for a total of 7 months.
|
|
Ear and labyrinth disorders
Paresthesia
|
2.8%
1/36 • Number of events 1 • Adverse events were collected from enrollment through 6 monthly cycles, and 30 days after the end of treatment, for a total of 7 months.
|
|
Reproductive system and breast disorders
Gynecomastia
|
2.8%
1/36 • Number of events 1 • Adverse events were collected from enrollment through 6 monthly cycles, and 30 days after the end of treatment, for a total of 7 months.
|
Additional Information
Dr. Neal D. Shore, MD, FACS, CPI
Carolina Research Professionals, LLC
Phone: 843-449-1010
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place