Radium(223) Dichloride (Alpharadin) in Castration-Resistant (Hormone-Refractory) Prostate Cancer Patients With Bone Metastases

Study Overview
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Brief Summary
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This study is a prospective, interventional, open-label, multi-center early access program for the use of Ra-223 Cl2 in HRPC/CRPC (Hormone refractory prostate cancer / Castrate resistant prostate cancer) patients diagnosed with bone metastasis and to collect additional short and long term safety data on the product.

Official Title
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Radium-223 Dichloride (Alpharadin) in Castration-Resistant (Hormone-Refractory) Prostate Cancer Patients With Bone Metastases

Conditions
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Prostatic Neoplasms

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years of age Histologically or cytologically confirmed prostate cancer Patients diagnosed with progressive bone predominant metastatic CRPC/HRPC (Hormone refractory prostate cancer / Castrate resistant prostate cancer) with at least 2 skeletal metastases on imaging with no lung, liver, and/or brain metastasis (lymph node only metastasis is allowed) Progressive disease is defined either by: The appearance of new bone lesions. If progression is based on new lesion(s) on imaging only without an increase in prostate specific antigen (PSA), PSA values from 3 assessments within the last 6 months must be provided; OR In the absence of new bone lesions by 2 subsequent increases in serum PSA over previous reference value, which should not be more than 6 months before screening, each measured at least 1 week apart with the last PSA ≥ 5 ng/mL. (The reference value time point 1, is defined as the last PSA measured before increases are documented, with subsequent values obtained a minimum of 1 week apart. If the PSA at time point 3 is greater than the PSA at time point 2, then eligibility has been met. If the PSA at time point 3 is not greater than the PSA at time point 2 but the PSA value at time point 4 and/or time point 5 is greater than the PSA at time point 2, the patient is eligible assuming that other criteria are met) Life expectancy ≥ 6 months Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 - 2 Adequate hematological, liver, and renal function Absolute neutrophil count (ANC) ≥ 1.5 x10^9/L Platelet count ≥ 100 x10^9/L Hemoglobin ≥ 10.0 g/dL (100 g/L; 6.2 mmol/L) Total bilirubin level ≤ 1.5 x institutional upper limit of normal (ULN) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN Creatinine ≤ 1.5 x ULN Albumin > 25 g/L Exclusion Criteria: Treatment with an investigational drug within previous 4 weeks, or planned during the treatment period or follow-up Eligible for first course of docetaxel, i.e., patients who are fit enough, willing, and who are located where treatment with docetaxel is available Treatment with cytotoxic chemotherapy within previous 4 weeks, or failure to recover from AEs (adverse events) due to cytotoxic chemotherapy administered more than 4 weeks previous (however, ongoing neuropathy is permitted) Prior hemibody external radiotherapy is excluded. Patients 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 with radionuclides (e.g., strontium-89, samarium-153, rhenium-186, or rhenium-188, or radium-223 dichloride) for the treatment of bony metastases 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 or pelvic computed tomography (CT) (or other imaging modality based on institutional standard of care) Presence of brain metastases Lymphadenopathy exceeding 6 cm in short-axis diameter Any size pelvic lymphadenopathy if it is thought to be a contributor to concurrent hydronephrosis Imminent or history of spinal cord compression based on clinical findings and/or magnetic resonance imaging (MRI). Patients with history of spinal cord compression should have completely recovered. Any other serious illness or medical condition, such as but not limited to: Any infection ≥ National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 Grade 2 Cardiac failure New York Heart Association (NYHA) III or IV Crohn's disease or ulcerative colitis Bone marrow dysplasia Fecal incontinence

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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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 (BAY88-8223)<br>* One injection to be administered every 4 weeks up to 6 injections. The dose per injection is 50 kBq/kg body weight.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute safety, variables will be summarized using descriptive statistics based on adverse events collection | Safety variables to be analyzed during the treatment period include: ECOG PS, Skeletal-related events, Treatment emergent Grade 3-4 AEs, any grade of treatment-related AEs and SAEs, Safety laboratory tests including hematology and serum chemistry | From baseline to 30 days post-treatment | 
| Long-term safety, variables will be summarized using descriptive statistics based on adverse events collection | Safety variables to be analyzed during the follow-up period include: Skeletal-related events, Treatment related AEs and SAEs, Secondary malignancies | From 30 days post-treatment up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brief Pain Inventory, as assessed by BPI-SF questionnaire (Brief Pain Inventory-Short Form) |  | From baseline up to 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Radium 223, Alpharadin, Prostate Cancer, Bone metastases, Castrate resistant prostate cancer, Hormone refractory prostate cancer