Phase 1, Open-label, Single Ascending-dose Study to Assess Safety, Pharmacokinetics, Biodistribution and Radiation Dosimetry of Intravenous Doses of Alpharadin™ Injection (Radium-223 Chloride) in Patients With HRPC and Skeletal Metastases
1. Must be ≥18 years of age.
2. Have histologically or cytologically evidence of adenocarcinoma of the prostate.
3. Have progressive castrate metastatic disease as shown by at least one of the
Radionuclide Bone Scan: New osseous lesions. MRI or CT: At least a 20% increase in
the sum of the LD of target lesions. or
A minimum of three rising PSA values from a baseline that are obtained 1 week or more
apart, or 2 measurements 2 or more weeks apart.
4. Have skeletal metastases confirmed by bone scintigraphy within the last 4 weeks.
Evidence of at least 2 bone metastases on bone scan.
5. Have castrate levels of testosterone (<50 ng/ml). Treatment to maintain castrate
levels of testosterone must be continued.
6. Patients who have failed initial hormonal therapy using either an orchiectomy or a
GnRH agonist in combination with an antiandrogen must first progress through
antiandrogen withdrawal prior to being eligible. The minimum timeframe to document
failure of anti-androgen withdrawal will be four weeks.
7. Have Karnofsky performance status ≥60%.
8. Have a life expectancy ≥6 months.
9. Have the following laboratory requirements:
- White Blood Count (WBC) ≥3,000/mm3
- Absolute Neutrophil Count (ANC) ≥1,500/ mm3
- Platelet (PLT) ≥100,000/ mm3
- Hemoglobin (HGB) ≥10 mg/dl
- Bilirubin ≤2.0 mg/dl (unless the patient has Gilbert's syndrome)
- AST and ALT ≤2,5 times upper institutional limit of the normal range
- Serum creatinine ≤2.0 mg/dl
10. Must be able and willing to sign an informed consent indicating that he is aware of
the investigational nature of this study in keeping with the policies of the
institution and have provided written authorization for use and disclosure of
protected health information.
11. Must be willing and able to comply with the protocol, and agrees to return to the
hospital for follow-up visits and examination.
1. Have received an investigational drug within 4 weeks prior to the administration of
Alpharadin, or is scheduled to receive one during the treatment and post-treatment
2. Have received chemo-, immunotherapy, or external radiotherapy within the last 4 weeks
prior to administration of study drug, or has not recovered from acute adverse events
as a result of such therapy.
3. Have received prior hemibody external radiotherapy*.
4. Have a need for immediate external radiotherapy.
5. Have received systemic radiotherapy with radium-223, strontium-89, samarium-153,
rhenium-186 or rhenium-188 for the treatment of bony metastases within the last 24
weeks prior to administration of study drug.
6. When receiving bisphosphonates, have changed the dose within 4 weeks before
administration of study drug.
7. Have started or stopped systemic steroids within a week prior to study drug
administration, or are expected to be subject to changes in the systemic steroid
8. Have imminent or established spinal cord compression based on clinical findings
9. Have other currently active (relapse within the last 3 years) malignancy (except
non-melanoma skin cancer) that are not prostate cancer metastases
10. Have small cell carcinoma.
11. Have predominant visceral metastases (≥ 3 lung or liver lesions) or symptomatic
lymph-adenopathy (scrotal or pedal edema).
12. Any other serious illness or medical condition, for example:
- any uncontrolled infection
- any patient who has clinical heart failure severe enough to cause marked
limitation of activity, and who is only comfortable at rest; or any patient who
has heart failure more severe than this (NYHA Heart Failure Class III or IV)
- Crohn's disease or ulcerative colitis