<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/NCT02199197</url>
  </required_header>
  <id_info>
    <org_study_id>HCI68770</org_study_id>
    <nct_id>NCT02199197</nct_id>
  </id_info>
  <brief_title>Radium Ra 223 With Enzalutamide Compared to Enzalutamide Alone in Men With Metastatic Castration Refractory Prostate Cancer</brief_title>
  <official_title>A Phase 2 Randomized Study Comparing Radium Ra 223 Dichloride Plus Enzalutamide With Enzalutamide Alone in Men With Metastatic Castration Refractory Prostate Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Utah</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Utah</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Study of Radium Ra 223 dichloride with enzalutamide compared to enzalutamide alone in men&#xD;
      with metastatic castration refractory prostate cancer&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 25, 2014</start_date>
  <completion_date type="Actual">October 3, 2019</completion_date>
  <primary_completion_date type="Actual">April 19, 2018</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Fold Change in Serum N-telopeptides From Baseline</measure>
    <time_frame>From prior to start of treatment to end of treatment or disease progression (approximately 6 months)</time_frame>
    <description>Patients had serum N-telopeptide labs drawn prior to the start of treatment and at the End of Treatment visit or at disease progression, whichever occurred first. The mean and standard deviation of the differences were calculated on a log 2 scale. Fold changes (post/pre) and 95% confidence intervals are reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With Adverse Events</measure>
    <time_frame>From first dose of study treatment to 30 days following last dose (approximately 7 months)</time_frame>
    <description>Adverse Events were assessed from start of Radium Ra 223 Dichloride or Enzalutamide treatment (whichever was started first) through 30 days after the last dose of either drug or until start of a new anti-cancer therapy, whichever came first. Adverse events were assessed using the Common Terminology for Adverse Events (CTCAE) version 4.0. Each event was assigned a grade (1-5), with lower grades indicating milder events. All adverse events were recorded, regardless of attribution to study treatment. Reported below are the number of patients who experienced any grade 3-5 non-hematological AE. A full listing of AEs affecting 5% or more participants are listed in the Adverse Events module of the Results section.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Prostate Specific Antigen (PSA) Progression Free Survival (PFS)</measure>
    <time_frame>Up to 2 years (24 months)</time_frame>
    <description>Prostate Specific Antigen (PSA) Progression Free Survival (PFS) is the time during with participants did not experience PSA progression. This is measured from the start of study therapy to the time of PSA progression. PSA progression is defined as a rise in PSA of at least 25% and at least 2 ng/ml from baseline or nadir. Kaplan-Meier methods were used.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Radiographic Progression Free Survival (PFS)</measure>
    <time_frame>Up to 2 years (24 months)</time_frame>
    <description>Radiographic Progression Free Survival (PFS) is the time during with participants did not experience disease progression based on study imaging. This is measured from the start of study therapy to the time of radiographic progression. Radiographic progression was defined by the Prostate Cancer Working Group 2 (PCWG2) criteria, in which soft tissue disease is evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and bone lesions are evaluated separately under PCWG2 criteria. PCWG2 and RECIST 1.1 are established radiographic assessment protocols. Kaplan-Meier methods were used.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bone Alkaline Phosphatase (ALP) Progression Free Survival (PFS)</measure>
    <time_frame>Up to 2 years (24 months)</time_frame>
    <description>Bone Alkaline Phosphatase (ALP) Progression Free Survival (PFS) is the time during with participants did not experience Bone ALP progression. This is measured from the start of study therapy to the time of Bone ALP progression. Bone ALP progression defined as a rise in Bone ALP of at least 25% and at least 2 micrograms (mcg)/L from baseline or nadir. Kaplan-Meier methods were used.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Count of Prostate Specific Antigen (PSA) Responses</measure>
    <time_frame>Up to 2 years after start of study treatment</time_frame>
    <description>Prostate Specific Antigen (PSA) Responses in participants were categorized based on decrease from baseline: less than 30% (&lt;30%) decrease (including increases from baseline), greater than or equal to 30% (&gt;=30%) decrease, greater than or equal to 50% (&gt;=50%) decrease, and greater than or equal to 90% (&gt;=90%) decrease. Count of participants in each category are provided</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Count of Radiographic Responses</measure>
    <time_frame>Up to 2 years after start of study treatment</time_frame>
    <description>Radiographic Responses in participants were assessed using the Prostate Cancer Working Group 2 (PCWG2) criteria. Possible responses include Complete Response (CR) (complete disappearance of all metastatic disease on imaging), Partial Response (PR) (improvement in metastatic disease on imaging), Stable Disease (SD) (neither worsening nor improvement of metastatic disease on imaging), and Progressive Disease (PD) (worsening of metastatic disease on imaging). A count of participants in each category is provided here.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>Up to 40 months</time_frame>
    <description>Overall Survival (OS) is the time during which participants did not pass away. This is measured from the start of study therapy to the time of death from any cause. Kaplan-Meier methods were used.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">49</enrollment>
  <condition>Prostate Cancer</condition>
  <arm_group>
    <arm_group_label>Radium Ra 223 Dichloride and Enzalutamide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Radium Ra 223 Dichloride and Enzalutamide administered concurrently for 6 28-day cycles.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Enzalutamide alone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Enzalutamide administered as a single agent for 6 28-day cycles.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Radium Ra 223 Dichloride</intervention_name>
    <description>Radium Ra 223 Dichloride, 55 kilobecquerel (kBq)/kg body weight, administered as a bolus intravenous (IV) injection (up to 1 minute) on Day 1 of each cycle for 6 cycles.</description>
    <arm_group_label>Radium Ra 223 Dichloride and Enzalutamide</arm_group_label>
    <other_name>Xofigo</other_name>
    <other_name>Alpharadin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Enzalutamide</intervention_name>
    <description>Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.</description>
    <arm_group_label>Enzalutamide alone</arm_group_label>
    <arm_group_label>Radium Ra 223 Dichloride and Enzalutamide</arm_group_label>
    <other_name>Xtandi</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically documented adenocarcinoma of the prostate.&#xD;
&#xD;
          -  Men at least 18 years of age and life expectancy of greater than or equal to 6 months.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.&#xD;
&#xD;
          -  Metastatic disease as evidenced by both lymphadenopathy and bony metastases or just&#xD;
             bony metastases on baseline bone scan and/or computed tomography (CT) scan or MRI of&#xD;
             the abdomen and pelvis within 28 days of registration. Chest imaging is only required&#xD;
             if clinically indicated or if there is known disease in the chest.&#xD;
&#xD;
          -  Castration resistant prostatic adenocarcinoma. Subjects must have castrate levels of&#xD;
             serum testosterone (less than 50 ng/dL) achieved by orchiectomy or luteinizing&#xD;
             hormone-releasing hormone (LHRH) agonist or antagonist therapy.&#xD;
&#xD;
          -  Previously received docetaxel or are not healthy enough per clinical judgment or&#xD;
             declined to receive it&#xD;
&#xD;
          -  Evidence of disease progression on or after the most recent systemic treatment defined&#xD;
             by the following criteria:&#xD;
&#xD;
               -  Prostate-Specific Antigen (PSA): Increasing serum PSA levels as defined by the&#xD;
                  Prostate Cancer Working Group 2 (PCWG2), determined by 2 consecutive measurements&#xD;
                  (compared to a baseline or nadir value). If the third measurement is below the&#xD;
                  second, then a fourth measurement must be greater than the second. The confirming&#xD;
                  third or fourth measurement must be greater or equal to 2 ng/mL. PSA progression&#xD;
                  must have occurred within 15 months of registration (with at least 7 days between&#xD;
                  each PSA measurement). Additionally, the PSA progression as described above&#xD;
                  should have occurred during or after the most recent systemic treatment for&#xD;
                  prostate cancer.&#xD;
&#xD;
               -  Measurable disease: greater than or equal to 20% increase in the sum of the short&#xD;
                  axis diameter of all measurable lymph nodes or the development of any new&#xD;
                  measurable lymphadenopathy by RECIST 1.1 and PCWG2 criteria.&#xD;
&#xD;
               -  Non-measurable disease:&#xD;
&#xD;
          -  Lymph node disease: The appearance of 1 or more new lymphadenopathy, and/or&#xD;
             unequivocal worsening of non-measurable disease when compared to imaging studies&#xD;
             acquired during castration therapy or against the pre-castration studies if there was&#xD;
             no response.&#xD;
&#xD;
          -  Bone disease: Appearance of 2 or more new areas of abnormal uptake on bone scan when&#xD;
             compared to imaging studies acquired during castration therapy or against the&#xD;
             pre-castration studies if there was no response. Increased uptake of pre-existing&#xD;
             lesions on bone scan does not constitute progression.&#xD;
&#xD;
          -  Symptomatic bone metastases&#xD;
&#xD;
          -  Adequate hematologic, renal, and liver function as evidenced by laboratory test&#xD;
             results. (Transfusion of blood products are not allowed to normalize blood parameters&#xD;
             within 4 weeks of the first radium treatment.)&#xD;
&#xD;
          -  Subjects who have previously received docetaxel or are ineligible for docetaxel and&#xD;
             who are candidates for treatment with enzalutamide alone or enzalutamide in&#xD;
             combination with Radium-223&#xD;
&#xD;
          -  Men must agree to use adequate contraception beginning at the signing of the Informed&#xD;
             Consent Form until at least 6 months after the last dose of study drug. Because of the&#xD;
             potential side effect on spermatogenesis associated with radiation, men who are&#xD;
             sexually active must agree to use condoms and their female partners of reproductive&#xD;
             potential must agree to use a highly effective contraceptive method during and for 6&#xD;
             months after completing treatment.&#xD;
&#xD;
          -  Able to provide informed consent and have signed an approved consent form that&#xD;
             conforms to federal and institutional guidelines to ensure compliance with HIPAA&#xD;
             regulations.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  The presence of known brain metastases, malignant pleural effusions, or malignant&#xD;
             ascites. Brain MRI is required at screening only if clinically indicated.&#xD;
&#xD;
          -  Visceral metastases as assessed by chest, abdominal or pelvic computed tomography (CT)&#xD;
             (or other imaging modality)&#xD;
&#xD;
          -  Received systemic therapy with radionuclides (e.g., strontium-89, samarium-153,&#xD;
             rhenium-186, or rhenium-188, or Radium Ra 223 dichloride) for the treatment of bony&#xD;
             metastases&#xD;
&#xD;
          -  Prior treatment with enzalutamide.&#xD;
&#xD;
          -  Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery,&#xD;
             immunotherapy, biologic therapy, or tumor embolization) other than the protocol based&#xD;
             treatment. LHRH agonist or antagonist therapy, and supportive non-cancer directed&#xD;
             therapies like bisphosphonates or denosumab are allowed.&#xD;
&#xD;
          -  Prior cytoxic chemotherapy with the exception of docetaxel or cabazitaxel. Treatment&#xD;
             with docetaxel or cabazitaxel must be discontinued greater than 4 weeks from the time&#xD;
             of enrollment, and recovery of adverse events (AEs) to grade 1 or baseline (however,&#xD;
             ongoing neuropathy is permitted).&#xD;
&#xD;
          -  Major surgery within 30 days prior to start of study drug&#xD;
&#xD;
          -  Current, untreated pathologic long-bone fractures, imminent pathologic long-bone&#xD;
             fractures (cortical erosion on radiography greater than 50%).&#xD;
&#xD;
          -  Prior hemi-body external radiotherapy. Subjects who received other types of prior&#xD;
             external radiotherapy are allowed provided that bone marrow function is assessed and&#xD;
             meets the protocol requirements for hemoglobin, absolute neutrophil count (ANC), and&#xD;
             platelets.&#xD;
&#xD;
          -  Use of biologic response modifiers, such as granulocyte macrophage colony-stimulating&#xD;
             factor (GM-CSF) or granulocyte colony-stimulating factor (G-CSF) within 4 weeks prior&#xD;
             to screening&#xD;
&#xD;
          -  Lymphadenopathy exceeding 3 cm in short-axis diameter&#xD;
&#xD;
          -  Any size pelvic lymphadenopathy if it is thought to be a contributor to concurrent&#xD;
             hydronephrosis.&#xD;
&#xD;
          -  Current or imminent spinal cord compression based on clinical findings and/or magnetic&#xD;
             resonance imaging (MRI). Treatment should be completed for spinal cord compression.&#xD;
&#xD;
          -  Any other serious illness or medical condition in the opinion of the investigator,&#xD;
             such as but not limited to:&#xD;
&#xD;
          -  Any greater than or equal to Grade 2 infection as defined by NCI-CTCAE version 4.03.&#xD;
&#xD;
          -  Cardiac failure New York Heart Association (NYHA) III or IV&#xD;
&#xD;
          -  Crohn's disease or ulcerative colitis&#xD;
&#xD;
          -  Bone marrow dysplasia&#xD;
&#xD;
          -  Fecal incontinence&#xD;
&#xD;
          -  Concomitant use of narrow therapeutic index drugs that are metabolized by CYP3A4 (i.e.&#xD;
             alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide,&#xD;
             quinidine, sirolimus, tacrolimus), CYP2C9 (phenytoin, warfarin), and CYP2C19&#xD;
             (S-mephenytoin). [Note: Patients on stable doses of anti-coagulation with warfarin and&#xD;
             fentanyl will be eligible, as long as they are monitored closely with additional&#xD;
             international normalized ratio (INR) monitoring].&#xD;
&#xD;
          -  Any infection requiring parenteral antibiotic therapy or causing fever (temperature&#xD;
             greater than 100.5 degrees F or 38.1 degrees C) within 1 week prior to registration.&#xD;
&#xD;
          -  Concurrent other malignancy with the exception of: a) cutaneous squamous cell and&#xD;
             basal carcinomas, b) adequately treated stage 1-2 malignancy , c) adequately treated&#xD;
             stage 3-4 malignancy that had been in remission for greater than or equal to 2 years&#xD;
             at the time of registration.&#xD;
&#xD;
          -  Inability to comply with the protocol and/or not willing or not available for&#xD;
             follow-up assessments&#xD;
&#xD;
          -  Any medical intervention or other condition which, in the opinion of the Principal&#xD;
             Investigator could compromise adherence with study requirements or otherwise&#xD;
             compromise the study's objectives&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Huntsman Cancer Institute</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>April 22, 2014</study_first_submitted>
  <study_first_submitted_qc>July 23, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 24, 2014</study_first_posted>
  <results_first_submitted>April 19, 2019</results_first_submitted>
  <results_first_submitted_qc>May 20, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">May 21, 2019</results_first_posted>
  <last_update_submitted>October 5, 2020</last_update_submitted>
  <last_update_submitted_qc>October 5, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 30, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prostatic Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Radium Ra 223 dichloride</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>February 6, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/97/NCT02199197/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Radium Ra 223 Dichloride and Enzalutamide</title>
          <description>Radium Ra 223 Dichloride and Enzalutamide administered concurrently for 6 28-day cycles.&#xD;
Radium Ra 223 Dichloride: Radium Ra 223 Dichloride, 55 kilobecquerel (kBq)/kg body weight, administered as a bolus intravenous (IV) injection (up to 1 minute) on Day 1 of each cycle for 6 cycles.&#xD;
Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.</description>
        </group>
        <group group_id="P2">
          <title>Enzalutamide Alone</title>
          <description>Enzalutamide administered as a single agent for 6 28-day cycles.&#xD;
Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="35"/>
                <participants group_id="P2" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="35"/>
                <participants group_id="P2" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Radium Ra 223 Dichloride and Enzalutamide</title>
          <description>Radium Ra 223 Dichloride and Enzalutamide administered concurrently for 6 28-day cycles.&#xD;
Radium Ra 223 Dichloride: Radium Ra 223 Dichloride, 55 kBq/kg body weight, administered as a bolus intravenous (IV) injection (up to 1 minute) on Day 1 of each cycle for 6 cycles.&#xD;
Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.</description>
        </group>
        <group group_id="B2">
          <title>Enzalutamide Alone</title>
          <description>Enzalutamide administered as a single agent for 6 28-day cycles.&#xD;
Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="35"/>
            <count group_id="B2" value="14"/>
            <count group_id="B3" value="49"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="35"/>
                    <count group_id="B2" value="14"/>
                    <count group_id="B3" value="49"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="35"/>
                    <count group_id="B2" value="14"/>
                    <count group_id="B3" value="49"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="68.66" spread="8.20"/>
                    <measurement group_id="B2" value="68.64" spread="8.04"/>
                    <measurement group_id="B3" value="68.65" spread="8.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="35"/>
                    <count group_id="B2" value="14"/>
                    <count group_id="B3" value="49"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="69" lower_limit="55" upper_limit="85"/>
                    <measurement group_id="B2" value="69.5" lower_limit="54" upper_limit="81"/>
                    <measurement group_id="B3" value="69" lower_limit="54" upper_limit="85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="35"/>
                    <count group_id="B2" value="14"/>
                    <count group_id="B3" value="49"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="35"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="35"/>
                    <count group_id="B2" value="14"/>
                    <count group_id="B3" value="49"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="34"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="48"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="35"/>
                    <count group_id="B2" value="14"/>
                    <count group_id="B3" value="49"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="34"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="48"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Serum N-Telopeptide Levels (Log2 scale)</title>
          <population>Two patients on the Enzalutamide only arm did not have subsequent N-Telopeptide labs drawn and were excluded from the N-Telopeptide analysis, so are excluded here as well.</population>
          <units>nM BCE</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="35"/>
                    <count group_id="B2" value="12"/>
                    <count group_id="B3" value="47"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3.42" lower_limit="2.41" upper_limit="4.68"/>
                    <measurement group_id="B2" value="3.41" lower_limit="2.77" upper_limit="4.3"/>
                    <measurement group_id="B3" value="3.42" lower_limit="2.41" upper_limit="4.68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Fold Change in Serum N-telopeptides From Baseline</title>
        <description>Patients had serum N-telopeptide labs drawn prior to the start of treatment and at the End of Treatment visit or at disease progression, whichever occurred first. The mean and standard deviation of the differences were calculated on a log 2 scale. Fold changes (post/pre) and 95% confidence intervals are reported.</description>
        <time_frame>From prior to start of treatment to end of treatment or disease progression (approximately 6 months)</time_frame>
        <population>Per study protocol, only randomized patients with bone marker level measurements at baseline and Cycle 3 Day 1 will be evaluable for the primary efficacy outcome. 8 patients were assigned to Radium + Enzalutamide without randomization and were excluded from analysis. 2 patients on Enzalutamide alone did not reach Cycle 3 Day 1 and were excluded.</population>
        <group_list>
          <group group_id="O1">
            <title>Radium Ra 223 Dichloride and Enzalutamide</title>
            <description>Radium Ra 223 Dichloride and Enzalutamide administered concurrently for 6 28-day cycles.&#xD;
Radium Ra 223 Dichloride: Radium Ra 223 Dichloride, 55 kBq/kg body weight, administered as a bolus intravenous (IV) injection (up to 1 minute) on Day 1 of each cycle for 6 cycles.&#xD;
Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.</description>
          </group>
          <group group_id="O2">
            <title>Enzalutamide Alone</title>
            <description>Enzalutamide administered as a single agent for 6 28-day cycles.&#xD;
Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.</description>
          </group>
        </group_list>
        <measure>
          <title>Fold Change in Serum N-telopeptides From Baseline</title>
          <description>Patients had serum N-telopeptide labs drawn prior to the start of treatment and at the End of Treatment visit or at disease progression, whichever occurred first. The mean and standard deviation of the differences were calculated on a log 2 scale. Fold changes (post/pre) and 95% confidence intervals are reported.</description>
          <population>Per study protocol, only randomized patients with bone marker level measurements at baseline and Cycle 3 Day 1 will be evaluable for the primary efficacy outcome. 8 patients were assigned to Radium + Enzalutamide without randomization and were excluded from analysis. 2 patients on Enzalutamide alone did not reach Cycle 3 Day 1 and were excluded.</population>
          <units>fold change</units>
          <param>Geometric Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.85" lower_limit="0.76" upper_limit="0.94"/>
                    <measurement group_id="O2" value="1.34" lower_limit="0.99" upper_limit="1.81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Adverse Events</title>
        <description>Adverse Events were assessed from start of Radium Ra 223 Dichloride or Enzalutamide treatment (whichever was started first) through 30 days after the last dose of either drug or until start of a new anti-cancer therapy, whichever came first. Adverse events were assessed using the Common Terminology for Adverse Events (CTCAE) version 4.0. Each event was assigned a grade (1-5), with lower grades indicating milder events. All adverse events were recorded, regardless of attribution to study treatment. Reported below are the number of patients who experienced any grade 3-5 non-hematological AE. A full listing of AEs affecting 5% or more participants are listed in the Adverse Events module of the Results section.</description>
        <time_frame>From first dose of study treatment to 30 days following last dose (approximately 7 months)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Radium Ra 223 Dichloride and Enzalutamide</title>
            <description>Radium Ra 223 Dichloride and Enzalutamide administered concurrently for 6 28-day cycles.&#xD;
Radium Ra 223 Dichloride: Radium Ra 223 Dichloride, 55 kBq/kg body weight, administered as a bolus intravenous (IV) injection (up to 1 minute) on Day 1 of each cycle for 6 cycles.&#xD;
Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.</description>
          </group>
          <group group_id="O2">
            <title>Enzalutamide Alone</title>
            <description>Enzalutamide administered as a single agent for 6 28-day cycles.&#xD;
Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Adverse Events</title>
          <description>Adverse Events were assessed from start of Radium Ra 223 Dichloride or Enzalutamide treatment (whichever was started first) through 30 days after the last dose of either drug or until start of a new anti-cancer therapy, whichever came first. Adverse events were assessed using the Common Terminology for Adverse Events (CTCAE) version 4.0. Each event was assigned a grade (1-5), with lower grades indicating milder events. All adverse events were recorded, regardless of attribution to study treatment. Reported below are the number of patients who experienced any grade 3-5 non-hematological AE. A full listing of AEs affecting 5% or more participants are listed in the Adverse Events module of the Results section.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="35"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Prostate Specific Antigen (PSA) Progression Free Survival (PFS)</title>
        <description>Prostate Specific Antigen (PSA) Progression Free Survival (PFS) is the time during with participants did not experience PSA progression. This is measured from the start of study therapy to the time of PSA progression. PSA progression is defined as a rise in PSA of at least 25% and at least 2 ng/ml from baseline or nadir. Kaplan-Meier methods were used.</description>
        <time_frame>Up to 2 years (24 months)</time_frame>
        <population>Two participants who dropped out prior to Cycle 3 were excluded from analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Radium Ra 223 Dichloride and Enzalutamide</title>
            <description>Radium Ra 223 Dichloride and Enzalutamide administered concurrently for 6 28-day cycles.&#xD;
Radium Ra 223 Dichloride: Radium Ra 223 Dichloride, 55 kilobecquerel (kBq)/kg body weight, administered as a bolus intravenous (IV) injection (up to 1 minute) on Day 1 of each cycle for 6 cycles.&#xD;
Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.</description>
          </group>
          <group group_id="O2">
            <title>Enzalutamide Alone</title>
            <description>Enzalutamide administered as a single agent for 6 28-day cycles.&#xD;
Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.</description>
          </group>
        </group_list>
        <measure>
          <title>Prostate Specific Antigen (PSA) Progression Free Survival (PFS)</title>
          <description>Prostate Specific Antigen (PSA) Progression Free Survival (PFS) is the time during with participants did not experience PSA progression. This is measured from the start of study therapy to the time of PSA progression. PSA progression is defined as a rise in PSA of at least 25% and at least 2 ng/ml from baseline or nadir. Kaplan-Meier methods were used.</description>
          <population>Two participants who dropped out prior to Cycle 3 were excluded from analysis</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="35"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.86" lower_limit="4.67" upper_limit="22.5"/>
                    <measurement group_id="O2" value="3.34" lower_limit="2.66" upper_limit="NA">Value is infinity because there were too few participants to get a real number.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Radiographic Progression Free Survival (PFS)</title>
        <description>Radiographic Progression Free Survival (PFS) is the time during with participants did not experience disease progression based on study imaging. This is measured from the start of study therapy to the time of radiographic progression. Radiographic progression was defined by the Prostate Cancer Working Group 2 (PCWG2) criteria, in which soft tissue disease is evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and bone lesions are evaluated separately under PCWG2 criteria. PCWG2 and RECIST 1.1 are established radiographic assessment protocols. Kaplan-Meier methods were used.</description>
        <time_frame>Up to 2 years (24 months)</time_frame>
        <population>Two participants who dropped out prior to Cycle 3 were excluded from analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Radium Ra 223 Dichloride and Enzalutamide</title>
            <description>Radium Ra 223 Dichloride and Enzalutamide administered concurrently for 6 28-day cycles.&#xD;
Radium Ra 223 Dichloride: Radium Ra 223 Dichloride, 55 kilobecquerel (kBq)/kg body weight, administered as a bolus intravenous (IV) injection (up to 1 minute) on Day 1 of each cycle for 6 cycles.&#xD;
Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.</description>
          </group>
          <group group_id="O2">
            <title>Enzalutamide Alone</title>
            <description>Enzalutamide administered as a single agent for 6 28-day cycles.&#xD;
Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.</description>
          </group>
        </group_list>
        <measure>
          <title>Radiographic Progression Free Survival (PFS)</title>
          <description>Radiographic Progression Free Survival (PFS) is the time during with participants did not experience disease progression based on study imaging. This is measured from the start of study therapy to the time of radiographic progression. Radiographic progression was defined by the Prostate Cancer Working Group 2 (PCWG2) criteria, in which soft tissue disease is evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and bone lesions are evaluated separately under PCWG2 criteria. PCWG2 and RECIST 1.1 are established radiographic assessment protocols. Kaplan-Meier methods were used.</description>
          <population>Two participants who dropped out prior to Cycle 3 were excluded from analysis</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="35"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.31" lower_limit="9.07" upper_limit="NA">Value is infinity because there were too few participants to get a real number.</measurement>
                    <measurement group_id="O2" value="5.62" lower_limit="2.76" upper_limit="NA">Value is infinity because there were too few participants to get a real number.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Bone Alkaline Phosphatase (ALP) Progression Free Survival (PFS)</title>
        <description>Bone Alkaline Phosphatase (ALP) Progression Free Survival (PFS) is the time during with participants did not experience Bone ALP progression. This is measured from the start of study therapy to the time of Bone ALP progression. Bone ALP progression defined as a rise in Bone ALP of at least 25% and at least 2 micrograms (mcg)/L from baseline or nadir. Kaplan-Meier methods were used.</description>
        <time_frame>Up to 2 years (24 months)</time_frame>
        <population>Two participants who dropped out prior to Cycle 3 were excluded from analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Radium Ra 223 Dichloride and Enzalutamide</title>
            <description>Radium Ra 223 Dichloride and Enzalutamide administered concurrently for 6 28-day cycles.&#xD;
Radium Ra 223 Dichloride: Radium Ra 223 Dichloride, 55 kilobecquerel (kBq)/kg body weight, administered as a bolus intravenous (IV) injection (up to 1 minute) on Day 1 of each cycle for 6 cycles.&#xD;
Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.</description>
          </group>
          <group group_id="O2">
            <title>Enzalutamide Alone</title>
            <description>Enzalutamide administered as a single agent for 6 28-day cycles.&#xD;
Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.</description>
          </group>
        </group_list>
        <measure>
          <title>Bone Alkaline Phosphatase (ALP) Progression Free Survival (PFS)</title>
          <description>Bone Alkaline Phosphatase (ALP) Progression Free Survival (PFS) is the time during with participants did not experience Bone ALP progression. This is measured from the start of study therapy to the time of Bone ALP progression. Bone ALP progression defined as a rise in Bone ALP of at least 25% and at least 2 micrograms (mcg)/L from baseline or nadir. Kaplan-Meier methods were used.</description>
          <population>Two participants who dropped out prior to Cycle 3 were excluded from analysis</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="35"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="NA" upper_limit="NA">Too few participants demonstrated Bone ALP progression to obtain a median, and thus 95% confidence intervals are infinite.</measurement>
                    <measurement group_id="O2" value="4.64" lower_limit="2.76" upper_limit="NA">Value is infinity because there were too few participants to get a real number.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Count of Prostate Specific Antigen (PSA) Responses</title>
        <description>Prostate Specific Antigen (PSA) Responses in participants were categorized based on decrease from baseline: less than 30% (&lt;30%) decrease (including increases from baseline), greater than or equal to 30% (&gt;=30%) decrease, greater than or equal to 50% (&gt;=50%) decrease, and greater than or equal to 90% (&gt;=90%) decrease. Count of participants in each category are provided</description>
        <time_frame>Up to 2 years after start of study treatment</time_frame>
        <population>Two participants who dropped out prior to Cycle 3 were excluded from analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Radium Ra 223 Dichloride and Enzalutamide</title>
            <description>Radium Ra 223 Dichloride and Enzalutamide administered concurrently for 6 28-day cycles.&#xD;
Radium Ra 223 Dichloride: Radium Ra 223 Dichloride, 55 kilobecquerel (kBq)/kg body weight, administered as a bolus intravenous (IV) injection (up to 1 minute) on Day 1 of each cycle for 6 cycles.&#xD;
Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.</description>
          </group>
          <group group_id="O2">
            <title>Enzalutamide Alone</title>
            <description>Enzalutamide administered as a single agent for 6 28-day cycles.&#xD;
Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.</description>
          </group>
        </group_list>
        <measure>
          <title>Count of Prostate Specific Antigen (PSA) Responses</title>
          <description>Prostate Specific Antigen (PSA) Responses in participants were categorized based on decrease from baseline: less than 30% (&lt;30%) decrease (including increases from baseline), greater than or equal to 30% (&gt;=30%) decrease, greater than or equal to 50% (&gt;=50%) decrease, and greater than or equal to 90% (&gt;=90%) decrease. Count of participants in each category are provided</description>
          <population>Two participants who dropped out prior to Cycle 3 were excluded from analysis</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="35"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;30%</title>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=30%</title>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=50%</title>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=90%</title>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Count of Radiographic Responses</title>
        <description>Radiographic Responses in participants were assessed using the Prostate Cancer Working Group 2 (PCWG2) criteria. Possible responses include Complete Response (CR) (complete disappearance of all metastatic disease on imaging), Partial Response (PR) (improvement in metastatic disease on imaging), Stable Disease (SD) (neither worsening nor improvement of metastatic disease on imaging), and Progressive Disease (PD) (worsening of metastatic disease on imaging). A count of participants in each category is provided here.</description>
        <time_frame>Up to 2 years after start of study treatment</time_frame>
        <population>Two participants who dropped out prior to Cycle 3 were excluded from analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Radium Ra 223 Dichloride and Enzalutamide</title>
            <description>Radium Ra 223 Dichloride and Enzalutamide administered concurrently for 6 28-day cycles.&#xD;
Radium Ra 223 Dichloride: Radium Ra 223 Dichloride, 55 kilobecquerel (kBq)/kg body weight, administered as a bolus intravenous (IV) injection (up to 1 minute) on Day 1 of each cycle for 6 cycles.&#xD;
Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.</description>
          </group>
          <group group_id="O2">
            <title>Enzalutamide Alone</title>
            <description>Enzalutamide administered as a single agent for 6 28-day cycles.&#xD;
Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.</description>
          </group>
        </group_list>
        <measure>
          <title>Count of Radiographic Responses</title>
          <description>Radiographic Responses in participants were assessed using the Prostate Cancer Working Group 2 (PCWG2) criteria. Possible responses include Complete Response (CR) (complete disappearance of all metastatic disease on imaging), Partial Response (PR) (improvement in metastatic disease on imaging), Stable Disease (SD) (neither worsening nor improvement of metastatic disease on imaging), and Progressive Disease (PD) (worsening of metastatic disease on imaging). A count of participants in each category is provided here.</description>
          <population>Two participants who dropped out prior to Cycle 3 were excluded from analysis</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="35"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Complete Response (CR)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Partial Response (PR)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Stable Disease (SD)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="28"/>
                    <measurement group_id="O2" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Progressive Disease (PD)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival (OS)</title>
        <description>Overall Survival (OS) is the time during which participants did not pass away. This is measured from the start of study therapy to the time of death from any cause. Kaplan-Meier methods were used.</description>
        <time_frame>Up to 40 months</time_frame>
        <population>Two participants who dropped out prior to Cycle 3 were excluded from analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Radium Ra 223 Dichloride and Enzalutamide</title>
            <description>Radium Ra 223 Dichloride and Enzalutamide administered concurrently for 6 28-day cycles.&#xD;
Radium Ra 223 Dichloride: Radium Ra 223 Dichloride, 55 kilobecquerel (kBq)/kg body weight, administered as a bolus intravenous (IV) injection (up to 1 minute) on Day 1 of each cycle for 6 cycles.&#xD;
Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.</description>
          </group>
          <group group_id="O2">
            <title>Enzalutamide Alone</title>
            <description>Enzalutamide administered as a single agent for 6 28-day cycles.&#xD;
Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS)</title>
          <description>Overall Survival (OS) is the time during which participants did not pass away. This is measured from the start of study therapy to the time of death from any cause. Kaplan-Meier methods were used.</description>
          <population>Two participants who dropped out prior to Cycle 3 were excluded from analysis</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="35"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26.0" lower_limit="17.6" upper_limit="NA">Value is infinity because there were too few participants to get a real number.</measurement>
                    <measurement group_id="O2" value="21.0" lower_limit="16.6" upper_limit="NA">Value is infinity because there were too few participants to get a real number.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months).</time_frame>
      <desc>The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.</desc>
      <group_list>
        <group group_id="E1">
          <title>Radium Ra 223 Dichloride and Enzalutamide</title>
          <description>Radium Ra 223 Dichloride and Enzalutamide administered concurrently for 6 28-day cycles.&#xD;
Radium Ra 223 Dichloride: Radium Ra 223 Dichloride, 55 kBq/kg body weight, administered as a bolus intravenous (IV) injection (up to 1 minute) on Day 1 of each cycle for 6 cycles.&#xD;
Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.</description>
        </group>
        <group group_id="E2">
          <title>Enzalutamide Alone</title>
          <description>Enzalutamide administered as a single agent for 6 28-day cycles.&#xD;
Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastrointestinal disorders - Other</sub_title>
                <description>inguinal hernia</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaphylaxis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other</sub_title>
                <description>disease progression - metastatic prostate cancer</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="35" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="13" subjects_affected="9" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear and labyrinth disorders - Other</sub_title>
                <description>inner ear &quot;fullness&quot;; &quot;rattling in ears&quot; attributed to hearing loss</description>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Bloating</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="25" subjects_affected="19" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Gastroesophageal reflux disease</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders - Other</sub_title>
                <description>viral syndrome / food poisoning</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="23" subjects_affected="16" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Edema limbs</sub_title>
                <counts group_id="E1" events="7" subjects_affected="6" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Facial pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="20" subjects_affected="16" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Flu like symptoms</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Gum infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" events="38" subjects_affected="18" subjects_at_risk="35"/>
                <counts group_id="E2" events="6" subjects_affected="4" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="36" subjects_affected="14" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="9" subjects_affected="7" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" events="47" subjects_affected="20" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="12" subjects_affected="7" subjects_at_risk="35"/>
                <counts group_id="E2" events="5" subjects_affected="4" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="9" subjects_affected="7" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Generalized muscle weakness</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Muscle weakness lower limb</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Muscle weakness upper limb</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="35"/>
                <counts group_id="E2" events="6" subjects_affected="3" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="8" subjects_affected="4" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other</sub_title>
                <description>polyps found on colonoscopy; esophageal carcinoma</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Paresthesia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Psychiatric disorders - Other</sub_title>
                <description>fuzzy/foggy-headed</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Urinary frequency</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Urinary urgency</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Gynecomastia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Testicular pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Sore throat</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other</sub_title>
                <description>dog bite; hives</description>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Skin ulceration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hot flashes</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Data Manager</name_or_title>
      <organization>Huntsman Cancer Institute Research Compliance Office</organization>
      <phone>801-585-0601</phone>
      <email>compliance@hci.utah.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02199197
org study id: HCI68770
nct id: NCT02199197
lead sponsor: 
has dmc: Yes
Study of Radium Ra 223 dichloride with enzalutamide compared to enzalutamide alone in men
      with metastatic castration refractory prostate cancer
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Fold Change in Serum N-telopeptides From Baseline
time frame: From prior to start of treatment to end of treatment or disease progression (approximately 6 months)
description: Patients had serum N-telopeptide labs drawn prior to the start of treatment and at the End of Treatment visit or at disease progression, whichever occurred first. The mean and standard deviation of the differences were calculated on a log 2 scale. Fold changes (post/pre) and 95% confidence intervals are reported.
measure: Number of Participants With Adverse Events
time frame: From first dose of study treatment to 30 days following last dose (approximately 7 months)
description: Adverse Events were assessed from start of Radium Ra 223 Dichloride or Enzalutamide treatment (whichever was started first) through 30 days after the last dose of either drug or until start of a new anti-cancer therapy, whichever came first. Adverse events were assessed using the Common Terminology for Adverse Events (CTCAE) version 4.0. Each event was assigned a grade (1-5), with lower grades indicating milder events. All adverse events were recorded, regardless of attribution to study treatment. Reported below are the number of patients who experienced any grade 3-5 non-hematological AE. A full listing of AEs affecting 5% or more participants are listed in the Adverse Events module of the Results section.
measure: Prostate Specific Antigen (PSA) Progression Free Survival (PFS)
time frame: Up to 2 years (24 months)
description: Prostate Specific Antigen (PSA) Progression Free Survival (PFS) is the time during with participants did not experience PSA progression. This is measured from the start of study therapy to the time of PSA progression. PSA progression is defined as a rise in PSA of at least 25% and at least 2 ng/ml from baseline or nadir. Kaplan-Meier methods were used.
measure: Radiographic Progression Free Survival (PFS)
time frame: Up to 2 years (24 months)
description: Radiographic Progression Free Survival (PFS) is the time during with participants did not experience disease progression based on study imaging. This is measured from the start of study therapy to the time of radiographic progression. Radiographic progression was defined by the Prostate Cancer Working Group 2 (PCWG2) criteria, in which soft tissue disease is evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and bone lesions are evaluated separately under PCWG2 criteria. PCWG2 and RECIST 1.1 are established radiographic assessment protocols. Kaplan-Meier methods were used.
measure: Bone Alkaline Phosphatase (ALP) Progression Free Survival (PFS)
time frame: Up to 2 years (24 months)
description: Bone Alkaline Phosphatase (ALP) Progression Free Survival (PFS) is the time during with participants did not experience Bone ALP progression. This is measured from the start of study therapy to the time of Bone ALP progression. Bone ALP progression defined as a rise in Bone ALP of at least 25% and at least 2 micrograms (mcg)/L from baseline or nadir. Kaplan-Meier methods were used.
measure: Count of Prostate Specific Antigen (PSA) Responses
time frame: Up to 2 years after start of study treatment
description: Prostate Specific Antigen (PSA) Responses in participants were categorized based on decrease from baseline: less than 30% (<30%) decrease (including increases from baseline), greater than or equal to 30% (>=30%) decrease, greater than or equal to 50% (>=50%) decrease, and greater than or equal to 90% (>=90%) decrease. Count of participants in each category are provided
measure: Count of Radiographic Responses
time frame: Up to 2 years after start of study treatment
description: Radiographic Responses in participants were assessed using the Prostate Cancer Working Group 2 (PCWG2) criteria. Possible responses include Complete Response (CR) (complete disappearance of all metastatic disease on imaging), Partial Response (PR) (improvement in metastatic disease on imaging), Stable Disease (SD) (neither worsening nor improvement of metastatic disease on imaging), and Progressive Disease (PD) (worsening of metastatic disease on imaging). A count of participants in each category is provided here.
measure: Overall Survival (OS)
time frame: Up to 40 months
description: Overall Survival (OS) is the time during which participants did not pass away. This is measured from the start of study therapy to the time of death from any cause. Kaplan-Meier methods were used.
arm group label: Radium Ra 223 Dichloride and Enzalutamide
arm group type: Experimental
description: Radium Ra 223 Dichloride and Enzalutamide administered concurrently for 6 28-day cycles.
arm group label: Enzalutamide alone
arm group type: Active Comparator
description: Enzalutamide administered as a single agent for 6 28-day cycles.
intervention type: Drug
intervention name: Radium Ra 223 Dichloride
description: Radium Ra 223 Dichloride, 55 kilobecquerel (kBq)/kg body weight, administered as a bolus intravenous (IV) injection (up to 1 minute) on Day 1 of each cycle for 6 cycles.
arm group label: Radium Ra 223 Dichloride and Enzalutamide
other name: Xofigo
other name: Alpharadin
intervention type: Drug
intervention name: Enzalutamide
description: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.
arm group label: Enzalutamide alone
arm group label: Radium Ra 223 Dichloride and Enzalutamide
other name: Xtandi
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: United States
responsible party type: Sponsor
mesh term: Prostatic Neoplasms
mesh term: Radium Ra 223 dichloride
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 