Radium-223 Dichloride Asian Population Study in the Treatment of CRPC Patients With Bone Metastasis

Study Overview
=================
Brief Summary
-----------------
To evaluate the safety and efficacy (Overall survival [OS]) of multiple doses of Ra-223 dichloride in an Asian population of subjects with CRPC metastatic to the bone.

Official Title
-----------------
A Single-arm, International, Prospective, Interventional, Open-label, Multicenter Study of Radium-223 Dichloride in the Treatment of Patients With Castration-Resistant Prostate Cancer (CRPC) With Bone Metastasis.

Conditions
-----------------
Prostatic Neoplasms

Intervention / Treatment
-----------------
* Drug: Radium-223 dichloride (Xofigo, BAY88-8223)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically or cytologically confirmed adenocarcinoma of the prostate Patients diagnosed with progressive bone predominant metastatic Castration-Resistant Prostate Cancer (CRPC) /Hormone Refractory Prostate Cancer (HRPC) with at least 2 skeletal metastases on imaging with no lung, liver, and/or brain metastasis (lymph node only metastasis is allowed) Known hormone refractory disease No intention to use cytotoxic chemotherapy within the next 6 months Either regular (not occasional) analgesic medication use for cancer related bone pain or treatment with external bean radiation therapy (EBRT) for bone pain within previous 12 weeks Age >/= 18 years Race is Asian Eastern Co-operative Oncology Group (ECOG) Performance Status (PS): 0-2 Life expectancy >/= 6 months Adequate bone marrow, liver and renal function as assessed by the Laboratory required by protocol Exclusion Criteria: Treatment with an investigational drug within previous 4 weeks prior to screening, or planned during the treatment or follow-up periods Eligible for docetaxel treatment, i.e. subjects who are fit enough, willing and who are located where treatment with docetaxel is available Treatment with cytotoxic chemotherapy within previous 4 weeks prior to screening, or failure to recover from adverse events due to cytotoxic chemotherapy administered more than 4 weeks prior to screening (however ongoing neuropathy is permitted) Prior hemibody external radiotherapy is excluded. Subjects who received other types of prior external radiotherapy are allowed provided that the bone marrow function is assessed and meets the protocol requirements for hemoglobin, absolute neutrophil count and platelets. Received systemic therapy radionuclides (e.g., strontium-89, samarium-153, rhenium-186, rhenium-188, or radium-223 dichloride) for the treatment of bony metastases Blood transfusion or erythropoetin stimulating agents within the previous 4 weeks prior to screening Other malignancy treated within the last 3 years (except non-melanoma skin cancer or low-grade superficial bladder cancer) Visceral metastases as assessed by abdominal/pelvic computed tomography (CT) or other imaging modality Presence of brain metastases Lymphadenopathy exceeding 3 cm in short-axis diameter Any size pelvic lymphadenopathy if it is thought to be a contributor to concurrent hydronephrosis Imminent or established spinal cord compression based on clinical findings and/or magnetic resonance imaging (MRI). Subjects with history of spinal cord compression should have completely recovered. Received local practice implant therapy containing lodine-125 or Palladium-103 for the primary lesion of prostate cancer within the 6 months prior to screening. Any other serious illness or medical condition

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Radium-223 dichloride<br> | Drug: Radium-223 dichloride (Xofigo, BAY88-8223)<br>* Radium-223 dichloride, 55 kBq/kg body weight, will be administered as a slow bolus IV injection at 4 week intervals for up to 6 doses.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events as a measure of safety and tolerability |  | Up to 36 months | 
| Number of participants with laboratory changes |  | Up to 36 months | 
| Number of participants with changes in vital signs |  | Up to 36 months | 
| Number of participants with changes in electrocardiogram (ECG) |  | Up to 36 months | 
| Overall Survival (OS) | OS is defined as the time from date of first study drug treatment to death due to any cause. Subjects still alive at the time of analysis were censored at their last date of last contact. | Up to 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in total Alkaline Phosphate (ALP) in serum |  | Up to 36 months | 
| Number of participants with total-ALP normalization |  | Up to 36 months | 
| Time to total ALP progression |  | Up to 36 months | 
| Changes in prostate specific antigen (PSA) in serum |  | Up to 36 months | 
| Time to PSA progression |  | Up to 36 months | 
| Time to first skeletal related event (SRE) |  | Up to 36 months | 
| SRE free survival |  | Up to 36 months | 
| Time to occurrence of first use of radio-isotopes to relieve skeletal symptoms |  | Up to 36 months | 
| Time to occurrence of first start of any other anti-cancer treatment |  | Up to 36 months | 
| Time to occurrence of first deterioration of Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) |  | Up to 36 months | 
| Quality of life (QoL) | QoL is assessed by the scores got from the Functional Assessment of Cancer Therapy in subjects with prostate cancer (FACT-P) questionnaire, EuroQoL (EQ-5D) questionnaire, and the BPI-SF questionnaire. | Up to 36 months | 
| Time to pain progression |  | Up to 36 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Radium-223 Dichloride, Prostatic Neoplasms, Bone Metastasis