The Combination Therapy With Ra-223 and Enzalutamide

Study Overview
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Brief Summary
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This study is to evaluate preliminary efficacy of Ra-223 in combination with Enzalutamide in progressive CRPC patients with bone metastasis

Official Title
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The Study of Combination Therapy With Radium-223 and Enzalutamide in Osaka City University

Conditions
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Castration-resistant Prostate Cancer, Bone Metastases

Intervention / Treatment
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* Drug: Ra-223 in combination with enzalutamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients diagnosed as CRPC Surgical or those who will be treated with luteinizing hormone-releasing hormone (LHRH) agonists throughout the study period, Patients who had >30% of PSA response to enzalutamide prior to enrollment, Interval between PSA progression and enrollment is up to 3 months, With bone metastases (≥ 2 hot spots) on bone scintigraphy within previous 24 weeks, No intention to use anti-cancer chemotherapy within the next 6 months, Eastern Cooperative Oncology Group performance status (ECOG-PS): 0-1, Life expectancy ≥ 6 months, Laboratory requirements within 30 days before enrollment: Absolute neutrophil count (ANC) ≥ 1.5 x 10e9/L, Platelet count ≥ 100 x 10e9/L, Hemoglobin ≥ 10.0 g/dL, Total bilirubin level ≤1.5 institutional upper limit of normal (ULN), Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2.5 ULN, Creatinine ≤ 1.5ULN, and estimated glomerular filtration rate (GFR) ≥ 30 mL/min/1.73 m2, Age ≥ 20, Ability to understand and the willingness to sign a written informed consent (IC). Exclusion Criteria: Prior chemotherapy or planned treatment with chemotherapy, PSA progression within 3 months after initiation of enzalutamide Prior treatment with corticosteroids, estramustine or abiraterone acetate, Any systemic radiotherapy with strontium-89, samarium-153, rhenium-186 or rhenium-188 for the treatment of bone metastases, Had history of gastrointestinal bleeding or ulcer within 3 months prior to study entry, History of visceral metastasis, or presence of visceral metastasis detected by screening imaging examinations, History of or known brain metastasis, Malignant lymphadenopathy ≧1.5 cm in short axis, Imminent or established spinal cord compression based on clinical findings and/or MRI (Magnetic Resonance Imaging), Any other serious illness or medical condition Substance abuse, medical, psychological, or social conditions that might interfere with the subject's participation in the study or evaluation of the study Results Those who judged to be inappropriate by the principal investigator or co-investigator.

Ages Eligible for Study
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Minimum Age: 20 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 |
| --- | --- |
| Other: Ra-223 + Enzalutamide<br> | Drug: Ra-223 in combination with enzalutamide<br>* Ra-223 (55 kBq/kg i.v.) 6 injections at 4 weeks interval in combination with enzalutamide 160 mg per a day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Alkaline phosphatase (ALP) | Percentage of change from baseline to 6 months (or earlier for those who discontinue study therapy) | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerability of Radium-223 therapy | Proportion of patients who complete 6 times injections of radium-223 | 6 months | 
| Evaluation for bone metastasis by 18F-NaF-PET | Fractional decline of intensity of tracer uptake measured by SUVmax on 18F-NaF-PET at 1, 3, 6 months. | 1, 3, 6 months | 
| Evaluation for bone metastasis by bone scintigraphy | The change of Bone Scan Index (BSI) by bone scintigraphy at 1, 3, 6 months. | 1, 3, 6 months | 
| Overall Survival Rate | Overall Survival (OS) is defined as the time from the registration to death due to any cause, or censored at date last known alive. | 3 years | 
| Time to occurrence of Symptomatic Skeletal-related Events (SSEs) | Time to occurrence of SSEs are defined asthe time from registration to the date of the occurrence of SSEs (symptomatic fracture, surgery or radiation to bone, or spinal cord compression). | 1 year | 
| Time to occurrence of visceral metastasis | Time to occurrence of visceral metastasis was defined as the time from registration to the date of the occurrence of a visceral metastasis for each patient. | 1 year | 
| Time to initiation of cytotoxic chemotherapy | The time to initiation of cytotoxic chemotherapy is defined as the time from registration to the date of initiation of cytotoxic chemotherapy. | 1 year | 
| Changes in Prostate Specific Antigen (PSA) | Percent change in prostate-specific antigen (PSA) from baseline at 6 months. | 6 months | 
| Changes From Baseline for Brief Pain Inventory (BPI) | The change for the BPI-SF (Brief Pain Inventory-Short Form) score was calculated. | 6 months | 
| Changes From Baseline for Functional Assessment of Cancer Therapy - Prostate (FACT-P) | The change for the FACT-P TOI domain (physical and social well-being and prostate specific score) was calculated. | 6 months | 
| Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) | Number of participants with adverse events as a measure of safety and tolerability. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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castration-resistant prostate cancer, bone metastasis