<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03305224</url>
  </required_header>
  <id_info>
    <org_study_id>CORE-OCU</org_study_id>
    <nct_id>NCT03305224</nct_id>
  </id_info>
  <brief_title>The Combination Therapy With Ra-223 and Enzalutamide</brief_title>
  <acronym>CORE-OCU</acronym>
  <official_title>The Study of Combination Therapy With Radium-223 and Enzalutamide in Osaka City University</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Taro Iguchi, MD, PHD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Bayer Yakuhin, Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Osaka City University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is to evaluate preliminary efficacy of Ra-223 in combination with Enzalutamide in&#xD;
      progressive CRPC patients with bone metastasis&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">October 27, 2017</start_date>
  <completion_date type="Anticipated">March 31, 2022</completion_date>
  <primary_completion_date type="Anticipated">October 30, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in Alkaline phosphatase (ALP)</measure>
    <time_frame>6 months</time_frame>
    <description>Percentage of change from baseline to 6 months (or earlier for those who discontinue study therapy)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Tolerability of Radium-223 therapy</measure>
    <time_frame>6 months</time_frame>
    <description>Proportion of patients who complete 6 times injections of radium-223</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation for bone metastasis by 18F-NaF-PET</measure>
    <time_frame>1, 3, 6 months</time_frame>
    <description>Fractional decline of intensity of tracer uptake measured by SUVmax on 18F-NaF-PET at 1, 3, 6 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation for bone metastasis by bone scintigraphy</measure>
    <time_frame>1, 3, 6 months</time_frame>
    <description>The change of Bone Scan Index (BSI) by bone scintigraphy at 1, 3, 6 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival Rate</measure>
    <time_frame>3 years</time_frame>
    <description>Overall Survival (OS) is defined as the time from the registration to death due to any cause, or censored at date last known alive.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to occurrence of Symptomatic Skeletal-related Events (SSEs)</measure>
    <time_frame>1 year</time_frame>
    <description>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).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to occurrence of visceral metastasis</measure>
    <time_frame>1 year</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to initiation of cytotoxic chemotherapy</measure>
    <time_frame>1 year</time_frame>
    <description>The time to initiation of cytotoxic chemotherapy is defined as the time from registration to the date of initiation of cytotoxic chemotherapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Prostate Specific Antigen (PSA)</measure>
    <time_frame>6 months</time_frame>
    <description>Percent change in prostate-specific antigen (PSA) from baseline at 6 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes From Baseline for Brief Pain Inventory (BPI)</measure>
    <time_frame>6 months</time_frame>
    <description>The change for the BPI-SF (Brief Pain Inventory-Short Form) score was calculated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes From Baseline for Functional Assessment of Cancer Therapy - Prostate (FACT-P)</measure>
    <time_frame>6 months</time_frame>
    <description>The change for the FACT-P TOI domain (physical and social well-being and prostate specific score) was calculated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)</measure>
    <time_frame>6 months</time_frame>
    <description>Number of participants with adverse events as a measure of safety and tolerability.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Castration-resistant Prostate Cancer</condition>
  <condition>Bone Metastases</condition>
  <arm_group>
    <arm_group_label>Ra-223 + Enzalutamide</arm_group_label>
    <arm_group_type>Other</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ra-223 in combination with enzalutamide</intervention_name>
    <description>Ra-223 (55 kBq/kg i.v.) 6 injections at 4 weeks interval in combination with enzalutamide 160 mg per a day</description>
    <arm_group_label>Ra-223 + Enzalutamide</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients diagnosed as CRPC&#xD;
&#xD;
          2. Surgical or those who will be treated with luteinizing hormone-releasing hormone&#xD;
             (LHRH) agonists throughout the study period,&#xD;
&#xD;
          3. Patients who had &gt;30% of PSA response to enzalutamide prior to enrollment,&#xD;
&#xD;
          4. Interval between PSA progression and enrollment is up to 3 months,&#xD;
&#xD;
          5. With bone metastases (≥ 2 hot spots) on bone scintigraphy within previous 24 weeks,&#xD;
&#xD;
          6. No intention to use anti-cancer chemotherapy within the next 6 months,&#xD;
&#xD;
          7. Eastern Cooperative Oncology Group performance status (ECOG-PS): 0-1,&#xD;
&#xD;
          8. Life expectancy ≥ 6 months,&#xD;
&#xD;
          9. Laboratory requirements within 30 days before enrollment:&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) ≥ 1.5 x 10e9/L,&#xD;
&#xD;
               -  Platelet count ≥ 100 x 10e9/L,&#xD;
&#xD;
               -  Hemoglobin ≥ 10.0 g/dL,&#xD;
&#xD;
               -  Total bilirubin level ≤1.5 institutional upper limit of normal (ULN),&#xD;
&#xD;
               -  Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2.5 ULN,&#xD;
&#xD;
               -  Creatinine ≤ 1.5ULN, and estimated glomerular filtration rate (GFR) ≥ 30&#xD;
                  mL/min/1.73 m2,&#xD;
&#xD;
         10. Age ≥ 20,&#xD;
&#xD;
         11. Ability to understand and the willingness to sign a written informed consent (IC).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Prior chemotherapy or planned treatment with chemotherapy,&#xD;
&#xD;
          2. PSA progression within 3 months after initiation of enzalutamide&#xD;
&#xD;
          3. Prior treatment with corticosteroids, estramustine or abiraterone acetate,&#xD;
&#xD;
          4. Any systemic radiotherapy with strontium-89, samarium-153, rhenium-186 or rhenium-188&#xD;
             for the treatment of bone metastases,&#xD;
&#xD;
          5. Had history of gastrointestinal bleeding or ulcer within 3 months prior to study&#xD;
             entry,&#xD;
&#xD;
          6. History of visceral metastasis, or presence of visceral metastasis detected by&#xD;
             screening imaging examinations,&#xD;
&#xD;
          7. History of or known brain metastasis,&#xD;
&#xD;
          8. Malignant lymphadenopathy ≧1.5 cm in short axis,&#xD;
&#xD;
          9. Imminent or established spinal cord compression based on clinical findings and/or MRI&#xD;
             (Magnetic Resonance Imaging),&#xD;
&#xD;
         10. Any other serious illness or medical condition&#xD;
&#xD;
         11. Substance abuse, medical, psychological, or social conditions that might interfere&#xD;
             with the subject's participation in the study or evaluation of the study Results&#xD;
&#xD;
         12. Those who judged to be inappropriate by the principal investigator or co-investigator.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <gender_based>Yes</gender_based>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Osaka City University Graduate School of Medicine</name>
      <address>
        <city>Osaka</city>
        <zip>545-8585</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
  </location_countries>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>August 28, 2017</study_first_submitted>
  <study_first_submitted_qc>October 3, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 9, 2017</study_first_posted>
  <last_update_submitted>September 8, 2021</last_update_submitted>
  <last_update_submitted_qc>September 8, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 9, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Osaka City University</investigator_affiliation>
    <investigator_full_name>Taro Iguchi, MD, PHD</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>castration-resistant prostate cancer</keyword>
  <keyword>bone metastasis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prostatic Neoplasms</mesh_term>
    <mesh_term>Neoplasm Metastasis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03305224
org study id: CORE-OCU
nct id: NCT03305224
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
This study is to evaluate preliminary efficacy of Ra-223 in combination with Enzalutamide in
      progressive CRPC patients with bone metastasis
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Changes in Alkaline phosphatase (ALP)
time frame: 6 months
description: Percentage of change from baseline to 6 months (or earlier for those who discontinue study therapy)
measure: Tolerability of Radium-223 therapy
time frame: 6 months
description: Proportion of patients who complete 6 times injections of radium-223
measure: Evaluation for bone metastasis by 18F-NaF-PET
time frame: 1, 3, 6 months
description: Fractional decline of intensity of tracer uptake measured by SUVmax on 18F-NaF-PET at 1, 3, 6 months.
measure: Evaluation for bone metastasis by bone scintigraphy
time frame: 1, 3, 6 months
description: The change of Bone Scan Index (BSI) by bone scintigraphy at 1, 3, 6 months.
measure: Overall Survival Rate
time frame: 3 years
description: Overall Survival (OS) is defined as the time from the registration to death due to any cause, or censored at date last known alive.
measure: Time to occurrence of Symptomatic Skeletal-related Events (SSEs)
time frame: 1 year
description: 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).
measure: Time to occurrence of visceral metastasis
time frame: 1 year
description: 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.
measure: Time to initiation of cytotoxic chemotherapy
time frame: 1 year
description: The time to initiation of cytotoxic chemotherapy is defined as the time from registration to the date of initiation of cytotoxic chemotherapy.
measure: Changes in Prostate Specific Antigen (PSA)
time frame: 6 months
description: Percent change in prostate-specific antigen (PSA) from baseline at 6 months.
measure: Changes From Baseline for Brief Pain Inventory (BPI)
time frame: 6 months
description: The change for the BPI-SF (Brief Pain Inventory-Short Form) score was calculated.
measure: Changes From Baseline for Functional Assessment of Cancer Therapy - Prostate (FACT-P)
time frame: 6 months
description: The change for the FACT-P TOI domain (physical and social well-being and prostate specific score) was calculated.
measure: Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
time frame: 6 months
description: Number of participants with adverse events as a measure of safety and tolerability.
arm group label: Ra-223 + Enzalutamide
arm group type: Other
intervention type: Drug
intervention name: Ra-223 in combination with enzalutamide
description: Ra-223 (55 kBq/kg i.v.) 6 injections at 4 weeks interval in combination with enzalutamide 160 mg per a day
arm group label: Ra-223 + Enzalutamide
criteria: 
gender: Male
gender based: Yes
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Japan
responsible party type: Sponsor-Investigator
investigator affiliation: Osaka City University
investigator full name: Taro Iguchi, MD, PHD
investigator title: Principal Investigator
mesh term: Prostatic Neoplasms
mesh term: Neoplasm Metastasis
sharing ipd: No