<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/NCT02225704</url>
  </required_header>
  <id_info>
    <org_study_id>CTRIAL (ICORG) 13-21</org_study_id>
    <nct_id>NCT02225704</nct_id>
  </id_info>
  <brief_title>Radium-223 in Combination With Enzalutamide</brief_title>
  <official_title>A Phase II Study of Radium-223 in Combination With Enzalutamide in Progressive Metastatic Castrate-Resistant Prostate Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cancer Trials Ireland</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Cancer Trials Ireland</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study aims to determine the safety and tolerability of Radium-223 when administered in&#xD;
      combination with enzalutamide in progressive metastatic castrate-resistant prostate cancer.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 3, 2015</start_date>
  <completion_date type="Actual">November 23, 2021</completion_date>
  <primary_completion_date type="Actual">July 2017</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>To determine safety</measure>
    <time_frame>approximately 6 to 9 months</time_frame>
    <description>To record the incidence of grade 3 or higher adverse events during the period of combination therapy; graded according to the NCI CTCAE version 4</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to clinical and Prostate Specific Antigen (PSA) progression</measure>
    <time_frame>Approximately 2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PSA response</measure>
    <time_frame>approximately 2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to first skeletal-related event</measure>
    <time_frame>approximately 2 years</time_frame>
    <description>Time to first skeletal-related event will be analysed using the Kaplan-Meier method, presenting estimated of median PFS with 95% confidence intervals, also estimates of PFS and 95% confidence intervals at 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain assessment</measure>
    <time_frame>approximately 6 - 9 months</time_frame>
    <description>The Brief Pain Inventory - Short Form questionnaire will be used to gather this data</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measure overall survival</measure>
    <time_frame>approximately 2 years</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">45</enrollment>
  <condition>Prostate Cancer</condition>
  <arm_group>
    <arm_group_label>Radium-223 and enzalutamide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Radium-223 50kBq/kg by intravenous injection on day 1 of every 4 week cycle for maximum of 6 cycles Enzalutamide 160mg orally daily</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Radium-223 and enzalutamide</intervention_name>
    <arm_group_label>Radium-223 and enzalutamide</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Written informed consent obtained prior to any study-related procedures&#xD;
&#xD;
          2. Age ≥18 years and male.&#xD;
&#xD;
          3. ECOG performance status ≤ 2.&#xD;
&#xD;
          4. Histologically/cytologically confirmed adenocarcinoma of the prostate, and without&#xD;
             neuroendocrine differentiation or small cell histology.&#xD;
&#xD;
          5. Metastatic disease as confirmed by Computed tomography (CT)/ Magnetic resonance&#xD;
             imaging (MRI) or bone scan.&#xD;
&#xD;
          6. 6. Patients must have documented Progressive disease (PD) either by radiographic or&#xD;
             PSA criteria as defined in a) and b) below:&#xD;
&#xD;
               1. For the Radiographic PD assessment, 2 sets of scans using the same imaging&#xD;
                  modality (ie CT/MRI or bone scan) and taken at separate time points are required&#xD;
                  to document radiographic disease progression during or following the patient's&#xD;
                  most recent anti-neoplastic therapy, (note: the 1st bone scan can be from before&#xD;
                  most recent therapy but the 2nd scan must show disease progression during or&#xD;
                  after the most recent therapy).&#xD;
&#xD;
                  For patients with bone disease, progression will be assessed following&#xD;
                  recommendations by the Prostate Cancer Working Group (PCWG2, see Appendix FC):&#xD;
                  appearance of 2 or more new lesions on bone scan, confirmed, if necessary, by&#xD;
                  other imaging modalities (such as CT scan or MRI), if results of the bone scans&#xD;
                  are ambiguous).&#xD;
&#xD;
                  For patients with soft tissue lesions progression will be assessed using RECIST&#xD;
                  1.1 criteria, (see Appendix GD). Patients may have measurable or non-measurable&#xD;
                  disease according to RECIST criteria version 1.1 (see Appendix GD)&#xD;
&#xD;
               2. PSA progression is defined as an increase in PSA, as determined by 2 separate&#xD;
                  measurements taken at least 1 week apart and confirmed by a third. If the third&#xD;
                  measurement is not greater than the second measurement, then a fourth measurement&#xD;
                  must be taken and must be greater than the second measurement for the patient to&#xD;
                  be eligible for the study. Furthermore, the confirmatory PSA measurement (i.e.&#xD;
                  the third or, if applicable, fourth PSA measurement) must be defined. If a&#xD;
                  patient has received prior anti-androgen therapy (e.g. bicalutamide), PSA&#xD;
                  progression must be evident and documented after discontinuation of anti-androgen&#xD;
                  therapy, (note: The 1st PSA reading taken to document disease progression when&#xD;
                  the patient presents can be while the patient is on Casodex or other ADT).&#xD;
&#xD;
          7. Prior surgical castration or concurrent use of an agent for medical castration with&#xD;
             testosterone at screening less than 50ng/dL.&#xD;
&#xD;
          8. Screening PSA ≥ 2 ng/mL.&#xD;
&#xD;
          9. Patients, even if surgically sterilized who (i.e. status post-vasectomy):&#xD;
&#xD;
               -  will abstain from intercourse&#xD;
&#xD;
               -  or must agree to use barrier contraception during and for 6 months after&#xD;
                  discontinuation of study treatment.&#xD;
&#xD;
               -  If the patient engages in sexual intercourse with a woman of childbearing&#xD;
                  potential, a condom and another form of birth control must be used during and for&#xD;
                  6 months after treatment.&#xD;
&#xD;
         10. Stable medical condition&#xD;
&#xD;
         11. Life expectancy of 12 months or more based on general health and prostate cancer&#xD;
             disease status as judged by the investigator.&#xD;
&#xD;
         12. Documented presence of osseous metastases with or without visceral involvement / lymph&#xD;
             nodes.&#xD;
&#xD;
         13. Able to swallow study drug as whole tablet.&#xD;
&#xD;
         14. Adequate haematological, hepatic, and renal function.&#xD;
&#xD;
         15. Continuous daily use of oral prednisone, oral dexamethasone, or other systemic&#xD;
             corticosteroids is allowed prior to study entry but must be discontinued a minimum of&#xD;
             2 weeks prior to start of study treatment.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients should not be receiving any other investigational agents (within 30 days&#xD;
             prior to registration)&#xD;
&#xD;
          2. Patients with Gastrointestinal (GI) tract disease resulting in an inability to take&#xD;
             oral medication, malabsorption syndrome, a requirement for IV alimentation, prior&#xD;
             surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g.&#xD;
             Crohn's disease, ulcerative colitis).&#xD;
&#xD;
          3. Have current active hepatic or biliary disease&#xD;
&#xD;
          4. Prior therapy with orteronel, ketoconazole, aminoglutethimide, abiraterone or&#xD;
             enzalutamide&#xD;
&#xD;
          5. All anti-androgen therapy (including bicalutamide) is excluded within 6 weeks prior to&#xD;
             first dose of study drug. Any other therapies for prostate cancer, other than GnRH&#xD;
             analogue therapy, such as progesterone, medroxyprogesterone, progestins (megesterol),&#xD;
             or 5-alpha reductase inhibitors (eg, finasteride or dutasteride), must be discontinued&#xD;
             2 weeks before the first dose of study drug. [Bisphosphonates and Denosumab are&#xD;
             allowed concomitant medications].&#xD;
&#xD;
          6. Prior chemotherapy for prostate cancer with the exception of:&#xD;
&#xD;
               -  neoadjuvant/ adjuvant therapy as part of initial primary treatment for local&#xD;
                  disease that was completed 2 or more years prior to screening.&#xD;
&#xD;
               -  Patients who received prior docetaxol for castrate sensitive metastatic prostate&#xD;
                  cancer commencing with 120 days of ADT initation where total dose received did&#xD;
                  not exceed 450mg/m2&#xD;
&#xD;
          7. Prior exposure to bone directed radioisotope therapy, eg samarium 153, strontium 90;&#xD;
&#xD;
          8. Exposure to external beam radiation within 4 weeks prior to receiving the first dose&#xD;
             of study drug. In patients with untreated imminent or established spinal cord&#xD;
             compression, treatment with standard of care, as clinically indicated, should be&#xD;
             completed before starting treatment with Ra-223 dichloride (Xofigo®).&#xD;
&#xD;
          9. Diagnosis of or treatment for another systemic malignancy within 2 years before the&#xD;
             first dose of study drug, or previously diagnosed with another malignancy and have any&#xD;
             evidence of residual disease.&#xD;
&#xD;
         10. History of myocardial infarction, unstable symptomatic ischemic heart disease/&#xD;
             unstable angina, uncontrolled on-going arrhythmias of Grade &gt;2 , pulmonary embolism,&#xD;
             or any other cardiac condition within 6 months prior to first dose of study drug.&#xD;
&#xD;
         11. New York Heart Association Class III or IV heart failure.&#xD;
&#xD;
         12. History of seizure, underlying brain injury with loss of consciousness, stroke,&#xD;
             transient ischaemic attack (TIA), cerebral vascular accident, primary brain tumours or&#xD;
             brain metastases, brain arteriovenous malformation, alcoholism., or the use of&#xD;
             concomitant medications that may lower the seizure threshold.&#xD;
&#xD;
         13. Known human immunodeficiency virus (HIV) infection, active chronic hepatitis B or C,&#xD;
             life-threatening illness unrelated to cancer, or any ongoing serious medical or&#xD;
             psychiatric illness that could, in the investigator's opinion, potentially interfere&#xD;
             with participation in this study. Patients will be tested for hepatitis B or C or HIV&#xD;
             infection during screening if they are considered by the investigator to be at higher&#xD;
             risk for these infections and have not been previously tested, or if testing is&#xD;
             required by the independent ethics committee or institutional review board.&#xD;
&#xD;
         14. Prohibited medications, including drugs that may affect exposure to enzalutamide i.e.&#xD;
             study drugs that induce or inhibit CYP3A4, CYP2C8, and CYP2C9&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ray McDermott, Prof</last_name>
    <role>Principal Investigator</role>
    <affiliation>St Vincent's University Hospital / AMNCH</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cork University Hospital</name>
      <address>
        <city>Cork</city>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mater Misericordiae University Hospital</name>
      <address>
        <city>Dublin 7</city>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mater Private Hospital</name>
      <address>
        <city>Dublin 7</city>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SLRON, St James's Hospital</name>
      <address>
        <city>Dublin</city>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St Vincents University Hospital / AMNCH</name>
      <address>
        <city>Dublin</city>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tallaght Hospital</name>
      <address>
        <city>Dublin</city>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Galway University Hospital</name>
      <address>
        <city>Galway</city>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Ireland</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>August 22, 2014</study_first_submitted>
  <study_first_submitted_qc>August 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 26, 2014</study_first_posted>
  <last_update_submitted>April 5, 2023</last_update_submitted>
  <last_update_submitted_qc>April 5, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 6, 2023</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>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02225704
org study id: CTRIAL (ICORG) 13-21
nct id: NCT02225704
lead sponsor: 
has dmc: No
This study aims to determine the safety and tolerability of Radium-223 when administered in
      combination with enzalutamide in progressive metastatic castrate-resistant prostate cancer.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: To determine safety
time frame: approximately 6 to 9 months
description: To record the incidence of grade 3 or higher adverse events during the period of combination therapy; graded according to the NCI CTCAE version 4
measure: Time to clinical and Prostate Specific Antigen (PSA) progression
time frame: Approximately 2 years
measure: PSA response
time frame: approximately 2 years
measure: Time to first skeletal-related event
time frame: approximately 2 years
description: Time to first skeletal-related event will be analysed using the Kaplan-Meier method, presenting estimated of median PFS with 95% confidence intervals, also estimates of PFS and 95% confidence intervals at 12 months
measure: Pain assessment
time frame: approximately 6 - 9 months
description: The Brief Pain Inventory - Short Form questionnaire will be used to gather this data
measure: Measure overall survival
time frame: approximately 2 years
arm group label: Radium-223 and enzalutamide
arm group type: Experimental
description: Radium-223 50kBq/kg by intravenous injection on day 1 of every 4 week cycle for maximum of 6 cycles Enzalutamide 160mg orally daily
intervention type: Drug
intervention name: Radium-223 and enzalutamide
arm group label: Radium-223 and enzalutamide
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ray McDermott, Prof
role: Principal Investigator
affiliation: St Vincent's University Hospital / AMNCH
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Ireland
responsible party type: Sponsor
mesh term: Prostatic Neoplasms