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

Bayer0 sites10 target enrollmentAugust 2008

ConditionsProstate Cancer Metastases Pharmacokinetics

InterventionsRadium-223 chloride (BAY88-8223)

DrugsRadium-223 chloride (BAY88-8223)

Overview

Phase: Phase 1
Intervention: Radium-223 chloride (BAY88-8223)
Conditions: Prostate Cancer
Sponsor: Bayer
Enrollment: 10
Primary Endpoint: All safety data, including adverse events, occurrence of treatment-emergent adverse events, changes in laboratory variables, vital signs, ECG, physical examination, long term radiation toxicity, including results of bone marrow biopsy
Status: Completed
Last Updated: 11 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Similar Trials

Overview

Brief Summary

The purpose of the study is to investigate the safety, biodistribution, radiation dosimetry and pharmacokinetics of three intravenous escalating dose levels of Xofigo (Alpharadin).

Detailed Description

Within the U.S., the trial is conducted under an IND sponsored by Bayer.

Registry

clinicaltrials.gov

Start Date

August 2008

End Date

October 2009

Last Updated

11 years ago

Study Type

Interventional

Study Design

Single Group

Sex

Male

Investigators

Sponsor

Bayer

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Must be ≥18 years of age
•Have histologically or cytologically evidence of adenocarcinoma of the prostate
•Have progressive castrate metastatic disease as shown by at least one of the following:
•Imaging modalities:
•Radionuclide Bone Scan: New osseous lesions
•MRI or CT: At least a 20% increase in the sum of the LD of target lesions OR
•Biochemical progression: 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
•Have skeletal metastases confirmed by bone scintigraphy within the last 4 weeks. Evidence of at least 2 bone metastases on bone scan.
•Have castrate levels of testosterone (\<50 ng/ml). Treatment to maintain castrate levels of testosterone must be continued.
•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.

Exclusion Criteria

•Have received an investigational drug within 4 weeks prior to the administration of Radium-223 chloride, or is scheduled to receive one during the treatment and post-treatment period
•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
•Have received prior hemibody external radiotherapy
•Have a need for immediate external radiotherapy
•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
•When receiving bisphosphonates, have changed the dose within 4 weeks before administration of study drug
•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 medication
•Have imminent or established spinal cord compression based on clinical findings and/or MRI
•Have other currently active (relapse within the last 3 years) malignancy (except non-melanoma skin cancer) that are not prostate cancer metastases
•Have small cell carcinoma

Arms & Interventions

Radium-223 chloride (Xofigo, BAY88-8223)

The patients will receive Radium-223 chloride as an escalating dose of either 50, 100 or 200 kBq/kg b.w. (0.0014, 0.0027 or 0.0054 mCi/kg).

Intervention: Radium-223 chloride (BAY88-8223)

Outcomes

Primary Outcomes

All safety data, including adverse events, occurrence of treatment-emergent adverse events, changes in laboratory variables, vital signs, ECG, physical examination, long term radiation toxicity, including results of bone marrow biopsy

Time Frame: 1 year

Biodistribution, dosimetry and pharmacokinetics (whole body activity assessment, the counts in region-of-interest (ROIs) from anterior and posterior whole-body images, and the assay of activity in blood

Time Frame: 6 days after injection

Secondary Outcomes

Circulating tumor cells (CTCs) enumeration and role of molecular profiling of CTC in predicting sensitivity to treatment and treatment response(1 year)
Post-treatment PSA effect: PSA decline, time to PSA progression after PSA response(1 year)
Post-treatment bone markers effect: Changes in bone marker values from pre- to post administration(1 year)