Dose Escalation Study of Radium-223 Dichloride in Patients With Advanced Skeletal Metastases

Recruitment & Eligibility

Inclusion Criteria

≥ 30 years of age
has histologically or cytologically confirmed breast or prostate carcinoma
presents with bony metastases, confirmed by scintigraphic imaging within the previous 4 weeks
relapsing with new foci in the skeleton after previous external radiotherapy
has a life expectancy of at least 8 weeks (study part Ia), 5 months for study part Ib
good performance status; ECOG (Eastern Cooperative Oncology Group) status 0-2
has normal bone marrow, hepatic, renal and cardiac functions
clinical chemical laboratory values are within pre-specified range, measured within 7 days prior to dosing day
for female patients: post-menopausal, surgically sterile or taking adequate contraceptive precaution

Exclusion Criteria

has previously been included in this study. This criterion is applicable for patients that receive a single injection of the study drug, but not for patients to be re-treated, or for those to receive a fractionated dosing regimen (study part Ib).
has received an investigational drug in the 4 weeks before or is scheduled to receiving one during or in the 8 weeks after study drug administration. This criterion is applicable for patients that receive a single injection of the study drug and for patients to be re-treated.
has received any other investigational drug than radium-223 in the 4 weeks before first injection of study drug or is scheduled to receiving one during or in the 8 weeks after the fractionated study drug regimen. This criterion is applicable for patients receiving fractionated dose of the study drug.
has received chemo-, immuno-, or radiotherapy within the last 4 weeks prior to entry in the study
has other active, serious, life-threatening disease with a life expectancy of less than 8 weeks
has any uncontrolled infection
requires oxygen for pulmonary metastases
has poor renal function with S-Creatinine >150 mmol/L (males), >100 mmol/L (females)
has heart insufficiency, Class III or IV NYHA (New York Heart Association)
is pregnant or lactating
for female patients: of childbearing potential, and not taking adequate contraceptive measures

Study & Design

Arm && Interventions

Group	Intervention	Description
Radium-223 dichloride	Radium-223 dichloride (BAY88-8223)	The study had 2 parts. Part 1a was designed with single injections of Radium-223 given to cohorts of 5 patients for each of 5 pre-defined dose levels. Part 1b was designed to retreat and fractionate the dose of Radium-223 in multiple injections.Based on the revised correction factor by calibration, recalculations verified that the single injection doses administered in the part 1a were : 46, 93, 163, 213 and 250 kBq/kg b.w. Two re-treated patients (dose group 6) received a second dose that resulted in a total dose of 250 kBq/kg b.w. The fractionated doses were 1/5 and ½ of the highest dose in part1b (i.e. 250kBq so 5 x 50 and 2 x 125 kBq/kg b.w. respectively).

Primary Outcome Measures

Name	Time	Method
Number of participants with predetermined adverse events (dose limiting toxicity [DLT]) as a measure of safety and tolerability while dose escalating	Up to 8 weeks from injection

Secondary Outcome Measures

Name	Time	Method
Blood clearance of radioactivity	48 hours after the last injection
Quality of Life Questionnaire	8 weeks after the last injection

Recruitment & Eligibility