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

A Phase I Open-label, Multicenter, Dose-escalating Study of Radium-223 in Patients With Advanced Skeletal Metastases

A new bone-seeking radiopharmaceutical drug, called Radium-223 dichloride (formerly known as "Alpharadin"), is currently under development. It is an injectable aqueous solution containing radium-223, a radionuclide that emits radiation of another quality and with a different distribution than radiopharmaceuticals currently in use.

After injection of the drug into the blood, a large portion of the drug will accumulate in the bones, and irradiate the skeletal metastases. The drug is expected to be retained longer in the painful sites of bone than in other sites of the body, and may alleviate pain through its radiation. Radium-223 is expected to be both efficacious as regards the targeted localised irradiation, and also to have a favourable safety profile.

The radiopharmaceutical drug Radium-223 has not been given to humans before. In this first clinical study in man, a so-called phase I study, the safety, tolerance and the toxicity of various radioactivity doses of Radium-223 will be evaluated.

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