Trial Outcomes & Findings for Phase I Dose Escalation of Monthly Intravenous Ra-223 Dichloride in Osteosarcoma (NCT NCT01833520)
NCT ID: NCT01833520
Last Updated: 2021-02-02
Results Overview
The goal of this initial study is to determine the safety of escalating doses of monthly Ra-223 dichloride in the number of osteosarcoma participants with osteoblastic bone-forming metastases until MTD or a dose 100 kBq/kg dose is reached (whichever is first).
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
18 participants
Primary outcome timeframe
3 months
Results posted on
2021-02-02
Participant Flow
Recruitment period: October 2013 to October 2015
Participant milestones
| Measure |
Escalation 50 kBq/kg
Radium-223 dichloride will be given monthly for up to 6 cycles and side effects of this bone-targeted therapy on monthly blood counts and alkaline phosphatase will be determined.
Ra-223 dichloride will be administered as a slow bolus IV injection at intervals of every 4 weeks for up to 6 cycles.
|
Escalation 75 kBq/kg
Radium-223 dichloride will be given monthly for up to 6 cycles and side effects of this bone-targeted therapy on monthly blood counts and alkaline phosphatase will be determined.
Ra-223 dichloride will be administered as a slow bolus IV injection at intervals of every 4 weeks for up to 6 cycles.
|
Escalation 100 kBq/kg
Radium-223 dichloride will be given monthly for up to 6 cycles and side effects of this bone-targeted therapy on monthly blood counts and alkaline phosphatase will be determined.
Ra-223 dichloride will be administered as a slow bolus IV injection at intervals of every 4 weeks for up to 6 cycles.
|
Expansion 100 kBq/kg
Radium-223 dichloride will be given monthly for up to 6 cycles and side effects of this bone-targeted therapy on monthly blood counts and alkaline phosphatase will be determined.
Ra-223 dichloride will be administered as a slow bolus IV injection at intervals of every 4 weeks for up to 6 cycles.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
3
|
3
|
9
|
3
|
|
Overall Study
COMPLETED
|
0
|
0
|
1
|
0
|
|
Overall Study
NOT COMPLETED
|
3
|
3
|
8
|
3
|
Reasons for withdrawal
| Measure |
Escalation 50 kBq/kg
Radium-223 dichloride will be given monthly for up to 6 cycles and side effects of this bone-targeted therapy on monthly blood counts and alkaline phosphatase will be determined.
Ra-223 dichloride will be administered as a slow bolus IV injection at intervals of every 4 weeks for up to 6 cycles.
|
Escalation 75 kBq/kg
Radium-223 dichloride will be given monthly for up to 6 cycles and side effects of this bone-targeted therapy on monthly blood counts and alkaline phosphatase will be determined.
Ra-223 dichloride will be administered as a slow bolus IV injection at intervals of every 4 weeks for up to 6 cycles.
|
Escalation 100 kBq/kg
Radium-223 dichloride will be given monthly for up to 6 cycles and side effects of this bone-targeted therapy on monthly blood counts and alkaline phosphatase will be determined.
Ra-223 dichloride will be administered as a slow bolus IV injection at intervals of every 4 weeks for up to 6 cycles.
|
Expansion 100 kBq/kg
Radium-223 dichloride will be given monthly for up to 6 cycles and side effects of this bone-targeted therapy on monthly blood counts and alkaline phosphatase will be determined.
Ra-223 dichloride will be administered as a slow bolus IV injection at intervals of every 4 weeks for up to 6 cycles.
|
|---|---|---|---|---|
|
Overall Study
Lack of Efficacy
|
3
|
3
|
8
|
3
|
Baseline Characteristics
Phase I Dose Escalation of Monthly Intravenous Ra-223 Dichloride in Osteosarcoma
Baseline characteristics by cohort
| Measure |
Escalation
n=15 Participants
Dose level: 50 kBq/kg, 75 kBq/kg and 100 kBq/kg. Radium-223 dichloride will be given monthly for up to 6 cycles and side effects of this bone-targeted therapy on monthly blood counts and alkaline phosphatase will be determined.
Ra-223 dichloride will be administered as a slow bolus IV injection at intervals of every 4 weeks for up to 6 cycles.
|
Expansion
n=3 Participants
Dose level: 100 kBq/kg. Radium-223 dichloride will be given monthly for up to 6 cycles and side effects of this bone-targeted therapy on monthly blood counts and alkaline phosphatase will be determined.
Ra-223 dichloride will be administered as a slow bolus IV injection at intervals of every 4 weeks for up to 6 cycles.
|
Total
n=18 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
5 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
9 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
11 Participants
n=206 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
15 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
12 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
12 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
15 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
18 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
15 participants
n=99 Participants
|
3 participants
n=107 Participants
|
18 participants
n=206 Participants
|
PRIMARY outcome
Timeframe: 3 monthsThe goal of this initial study is to determine the safety of escalating doses of monthly Ra-223 dichloride in the number of osteosarcoma participants with osteoblastic bone-forming metastases until MTD or a dose 100 kBq/kg dose is reached (whichever is first).
Outcome measures
| Measure |
Escalation 100 kBq/kg
n=9 Participants
Radium-223 dichloride will be given monthly for up to 6 cycles and side effects of this bone-targeted therapy on monthly blood counts and alkaline phosphatase will be determined.
Ra-223 dichloride will be administered as a slow bolus IV injection at intervals of every 4 weeks for up to 6 cycles.
|
Expansion 100 kBq/kg
n=3 Participants
Radium-223 dichloride will be given monthly for up to 6 cycles and side effects of this bone-targeted therapy on monthly blood counts and alkaline phosphatase will be determined.
Ra-223 dichloride will be administered as a slow bolus IV injection at intervals of every 4 weeks for up to 6 cycles.
|
Escalation 100 kBq/kg
Radium-223 dichloride will be given monthly for up to 6 cycles and side effects of this bone-targeted therapy on monthly blood counts and alkaline phosphatase will be determined.
Ra-223 dichloride will be administered as a slow bolus IV injection at intervals of every 4 weeks for up to 6 cycles.
|
Expansion 100 kBq/kg
Radium-223 dichloride will be given monthly for up to 6 cycles and side effects of this bone-targeted therapy on monthly blood counts and alkaline phosphatase will be determined.
Ra-223 dichloride will be administered as a slow bolus IV injection at intervals of every 4 weeks for up to 6 cycles.
|
|---|---|---|---|---|
|
Maximum Tolerated Dose (MTD) of Ra-223 Dichloride in Osteosarcoma
|
100 kBq/kg
|
100 kBq/kg
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, 3 months and 6 monthsAlkaline phosphatase reduction to quantitative imaging techniques (99mTc-MDP, 18FDG-PET-CT, 18FNa PET-CT scans) to determine objective response of osteosarcoma indicator lesions to 223-radium dichloride. \>30% increase in SUV peak indicates progression, if \>30% decrease in SUV peak indicates a response and other does not meet above criteria or mixed response using the NAFCIST and PERCIST criteria.
Outcome measures
| Measure |
Escalation 100 kBq/kg
n=2 Participants
Radium-223 dichloride will be given monthly for up to 6 cycles and side effects of this bone-targeted therapy on monthly blood counts and alkaline phosphatase will be determined.
Ra-223 dichloride will be administered as a slow bolus IV injection at intervals of every 4 weeks for up to 6 cycles.
|
Expansion 100 kBq/kg
n=3 Participants
Radium-223 dichloride will be given monthly for up to 6 cycles and side effects of this bone-targeted therapy on monthly blood counts and alkaline phosphatase will be determined.
Ra-223 dichloride will be administered as a slow bolus IV injection at intervals of every 4 weeks for up to 6 cycles.
|
Escalation 100 kBq/kg
n=6 Participants
Radium-223 dichloride will be given monthly for up to 6 cycles and side effects of this bone-targeted therapy on monthly blood counts and alkaline phosphatase will be determined.
Ra-223 dichloride will be administered as a slow bolus IV injection at intervals of every 4 weeks for up to 6 cycles.
|
Expansion 100 kBq/kg
n=3 Participants
Radium-223 dichloride will be given monthly for up to 6 cycles and side effects of this bone-targeted therapy on monthly blood counts and alkaline phosphatase will be determined.
Ra-223 dichloride will be administered as a slow bolus IV injection at intervals of every 4 weeks for up to 6 cycles.
|
|---|---|---|---|---|
|
Number of Participants With Objective Response of Osteosarcoma Indicator Lesions to 223-Radium Dichloride
>30% increase in SUV peak
|
2 Participants
|
0 Participants
|
3 Participants
|
2 Participants
|
|
Number of Participants With Objective Response of Osteosarcoma Indicator Lesions to 223-Radium Dichloride
>30% decrease in SUV peak
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Objective Response of Osteosarcoma Indicator Lesions to 223-Radium Dichloride
Other/Mixed Response
|
0 Participants
|
3 Participants
|
2 Participants
|
1 Participants
|
Adverse Events
Escalation 50 kBq/kg
Serious events: 1 serious events
Other events: 1 other events
Deaths: 2 deaths
Escalation 75 kBq/kg
Serious events: 1 serious events
Other events: 1 other events
Deaths: 2 deaths
Escalation 100 kBq/kg
Serious events: 2 serious events
Other events: 4 other events
Deaths: 5 deaths
Expansion 100 kBq/kg
Serious events: 3 serious events
Other events: 2 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Escalation 50 kBq/kg
n=3 participants at risk
Radium-223 dichloride will be given monthly for up to 6 cycles and side effects of this bone-targeted therapy on monthly blood counts and alkaline phosphatase will be determined.
Ra-223 dichloride will be administered as a slow bolus IV injection at intervals of every 4 weeks for up to 6 cycles.
|
Escalation 75 kBq/kg
n=3 participants at risk
Radium-223 dichloride will be given monthly for up to 6 cycles and side effects of this bone-targeted therapy on monthly blood counts and alkaline phosphatase will be determined.
Ra-223 dichloride will be administered as a slow bolus IV injection at intervals of every 4 weeks for up to 6 cycles.
|
Escalation 100 kBq/kg
n=9 participants at risk
Radium-223 dichloride will be given monthly for up to 6 cycles and side effects of this bone-targeted therapy on monthly blood counts and alkaline phosphatase will be determined.
Ra-223 dichloride will be administered as a slow bolus IV injection at intervals of every 4 weeks for up to 6 cycles.
|
Expansion 100 kBq/kg
n=3 participants at risk
Radium-223 dichloride will be given monthly for up to 6 cycles and side effects of this bone-targeted therapy on monthly blood counts and alkaline phosphatase will be determined.
Ra-223 dichloride will be administered as a slow bolus IV injection at intervals of every 4 weeks for up to 6 cycles.
|
|---|---|---|---|---|
|
Nervous system disorders
Peripheral motor neuropathy
|
33.3%
1/3 • 6 months
|
0.00%
0/3 • 6 months
|
0.00%
0/9 • 6 months
|
0.00%
0/3 • 6 months
|
|
Nervous system disorders
Seizure
|
0.00%
0/3 • 6 months
|
33.3%
1/3 • 6 months
|
0.00%
0/9 • 6 months
|
0.00%
0/3 • 6 months
|
|
General disorders
Neck pain
|
0.00%
0/3 • 6 months
|
0.00%
0/3 • 6 months
|
11.1%
1/9 • 6 months
|
0.00%
0/3 • 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Bronchopulmonary hemorhage
|
0.00%
0/3 • 6 months
|
0.00%
0/3 • 6 months
|
11.1%
1/9 • 6 months
|
0.00%
0/3 • 6 months
|
|
Blood and lymphatic system disorders
Anemia
|
0.00%
0/3 • 6 months
|
0.00%
0/3 • 6 months
|
11.1%
1/9 • 6 months
|
0.00%
0/3 • 6 months
|
|
Blood and lymphatic system disorders
Platelet count decreased
|
0.00%
0/3 • 6 months
|
0.00%
0/3 • 6 months
|
22.2%
2/9 • 6 months
|
0.00%
0/3 • 6 months
|
|
General disorders
Abdominal pain
|
0.00%
0/3 • 6 months
|
0.00%
0/3 • 6 months
|
11.1%
1/9 • 6 months
|
0.00%
0/3 • 6 months
|
|
Blood and lymphatic system disorders
Thromboembolic event
|
0.00%
0/3 • 6 months
|
0.00%
0/3 • 6 months
|
11.1%
1/9 • 6 months
|
0.00%
0/3 • 6 months
|
|
General disorders
Edema limbs
|
0.00%
0/3 • 6 months
|
0.00%
0/3 • 6 months
|
11.1%
1/9 • 6 months
|
0.00%
0/3 • 6 months
|
|
General disorders
Tumor pain
|
0.00%
0/3 • 6 months
|
0.00%
0/3 • 6 months
|
0.00%
0/9 • 6 months
|
33.3%
1/3 • 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.00%
0/3 • 6 months
|
0.00%
0/3 • 6 months
|
0.00%
0/9 • 6 months
|
33.3%
1/3 • 6 months
|
|
Endocrine disorders
Alkaline phophatase increased
|
0.00%
0/3 • 6 months
|
0.00%
0/3 • 6 months
|
0.00%
0/9 • 6 months
|
33.3%
1/3 • 6 months
|
|
General disorders
Pain in extremity
|
0.00%
0/3 • 6 months
|
0.00%
0/3 • 6 months
|
0.00%
0/9 • 6 months
|
33.3%
1/3 • 6 months
|
Other adverse events
| Measure |
Escalation 50 kBq/kg
n=3 participants at risk
Radium-223 dichloride will be given monthly for up to 6 cycles and side effects of this bone-targeted therapy on monthly blood counts and alkaline phosphatase will be determined.
Ra-223 dichloride will be administered as a slow bolus IV injection at intervals of every 4 weeks for up to 6 cycles.
|
Escalation 75 kBq/kg
n=3 participants at risk
Radium-223 dichloride will be given monthly for up to 6 cycles and side effects of this bone-targeted therapy on monthly blood counts and alkaline phosphatase will be determined.
Ra-223 dichloride will be administered as a slow bolus IV injection at intervals of every 4 weeks for up to 6 cycles.
|
Escalation 100 kBq/kg
n=9 participants at risk
Radium-223 dichloride will be given monthly for up to 6 cycles and side effects of this bone-targeted therapy on monthly blood counts and alkaline phosphatase will be determined.
Ra-223 dichloride will be administered as a slow bolus IV injection at intervals of every 4 weeks for up to 6 cycles.
|
Expansion 100 kBq/kg
n=3 participants at risk
Radium-223 dichloride will be given monthly for up to 6 cycles and side effects of this bone-targeted therapy on monthly blood counts and alkaline phosphatase will be determined.
Ra-223 dichloride will be administered as a slow bolus IV injection at intervals of every 4 weeks for up to 6 cycles.
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/3 • 6 months
|
0.00%
0/3 • 6 months
|
11.1%
1/9 • 6 months
|
0.00%
0/3 • 6 months
|
|
Blood and lymphatic system disorders
Anemia
|
0.00%
0/3 • 6 months
|
0.00%
0/3 • 6 months
|
33.3%
3/9 • 6 months
|
33.3%
1/3 • 6 months
|
|
General disorders
Fatigue
|
0.00%
0/3 • 6 months
|
0.00%
0/3 • 6 months
|
11.1%
1/9 • 6 months
|
33.3%
1/3 • 6 months
|
|
Blood and lymphatic system disorders
Lymphocyte count decreased
|
0.00%
0/3 • 6 months
|
0.00%
0/3 • 6 months
|
11.1%
1/9 • 6 months
|
0.00%
0/3 • 6 months
|
|
Skin and subcutaneous tissue disorders
Brittle nails
|
33.3%
1/3 • 6 months
|
0.00%
0/3 • 6 months
|
0.00%
0/9 • 6 months
|
0.00%
0/3 • 6 months
|
|
General disorders
Intermittent pain (jaw, neck, trunk, back)
|
0.00%
0/3 • 6 months
|
33.3%
1/3 • 6 months
|
0.00%
0/9 • 6 months
|
0.00%
0/3 • 6 months
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/3 • 6 months
|
0.00%
0/3 • 6 months
|
11.1%
1/9 • 6 months
|
0.00%
0/3 • 6 months
|
|
Blood and lymphatic system disorders
White Blood Cell decreased
|
0.00%
0/3 • 6 months
|
0.00%
0/3 • 6 months
|
44.4%
4/9 • 6 months
|
0.00%
0/3 • 6 months
|
|
General disorders
Bone pain
|
0.00%
0/3 • 6 months
|
0.00%
0/3 • 6 months
|
22.2%
2/9 • 6 months
|
0.00%
0/3 • 6 months
|
|
Blood and lymphatic system disorders
Neutrophil count decreased
|
0.00%
0/3 • 6 months
|
0.00%
0/3 • 6 months
|
11.1%
1/9 • 6 months
|
33.3%
1/3 • 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Bronchopulmonary hemorrhage
|
0.00%
0/3 • 6 months
|
0.00%
0/3 • 6 months
|
11.1%
1/9 • 6 months
|
0.00%
0/3 • 6 months
|
|
Blood and lymphatic system disorders
Platelet count decreased
|
0.00%
0/3 • 6 months
|
0.00%
0/3 • 6 months
|
44.4%
4/9 • 6 months
|
66.7%
2/3 • 6 months
|
Additional Information
Vivek Subbiah,Associate Professor, Invest. Cancer Therapeutics
UT MD Anderson Cancer Center
Phone: (713) 563-0393
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place