<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/NCT04489719</url>
  </required_header>
  <id_info>
    <org_study_id>RG1006011</org_study_id>
    <secondary_id>NCI-2020-04699</secondary_id>
    <secondary_id>10370</secondary_id>
    <nct_id>NCT04489719</nct_id>
  </id_info>
  <brief_title>Impact of DNA Repair Pathway Alterations on Sensitivity to Radium-223 in Bone Metastatic Castration-resistant Prostate Cancer</brief_title>
  <official_title>The Impact of DNA Repair Pathway Alterations Identified by Circulating Tumor DNA on Sensitivity to Radium-223 in Bone Metastatic Castration-Resistant Prostate Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Washington</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Bayer</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Washington</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study investigates how well radium-223 works in treating patients with&#xD;
      castration-resistant prostate cancer than has spread to the bones (bone metastases). Prostate&#xD;
      cancer is the most common cancer in men and the second leading cause of cancer death.&#xD;
      Furthermore, many men with notably advanced disease have been found to have abnormalities in&#xD;
      DNA repair. The purpose of this research is to study the role of a DNA repair pathway in&#xD;
      prostate cancer, specifically in response to administration of radium-223, an FDA-approved&#xD;
      drug known to cause DNA damage to cancerous cells. Understanding how defects in the DNA&#xD;
      repair pathway affects radium-223 treatment of prostate, may help doctors help plan effective&#xD;
      treatment in future patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      OUTLINE:&#xD;
&#xD;
      Patients receive standard of care radium Ra 223 dichloride given by intravenous (IV) bolus&#xD;
      every 4 weeks for up to 6 cycles. Patients undergo collection of blood every 1-3 months&#xD;
      during radium Ra 223 dichloride treatment.&#xD;
&#xD;
      After completion of study, patients are followed up every 3 months for up to 5 years from the&#xD;
      date of treatment completion.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 16, 2021</start_date>
  <completion_date type="Anticipated">August 1, 2028</completion_date>
  <primary_completion_date type="Anticipated">August 1, 2024</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Response rate</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>Response will be defined as having one or both of the following: confirmed prostate specific antigen (PSA) decline of &gt;= 30% from baseline AND/OR confirmed alkaline phosphatase (ALP) decline &gt;= 30% from baseline. Response is evaluated throughout the course of treatment until the post-radium-223 end of treatment laboratory studies. Confirmation of response by PSA and/or ALP requires a second consecutive value obtained &gt;= 2 weeks after the first with sustained &gt;= 30% decline. Characterization of response rate to radium-223 in the DRD patient population will be assessed by binomial proportion with Clopper-Pearson exact 2-sided 95% confidence intervals.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Response rate</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>Comparison of treatment response (outcome/dependent variable) between cases and controls will be assessed using multivariate logistic regression modelling adjusting for secondary variables as appropriate. Risk estimates will include odds ratios with 95% confidence intervals.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response rate in those with previous PARP inhibitor therapy</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>A multivariate logistic model with PARP inhibitor status as a secondary independent variable and a sensitivity analysis excluding those exposed to PARP inhibitors.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Survival by DRD status will be illustrated using univariate Kaplan-Meier curves. Additionally, Cox-PH model adjusting for age, Eastern Cooperative Oncology Group (ECOG) performance status, Gleason grade score, baseline ALP, PSA, hemoglobin (HB), and lactate dehydrogenase (LDH) will be performed. This analysis may be limited by expected small number of events, thus it may be limited to raw reporting of events by DRD status.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of radium Ra 223 dichloride</measure>
    <time_frame>Up to 6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain assessment</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>Assessed via Brief Pain Inventory survey</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Analgesic usage</measure>
    <time_frame>Up to 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life (FACT-P survey)</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>Assessed via FACT-P quality of life survey</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>To access risk of adverse events by DRD status, 2 logistic models will be used. The first will classify the dependent variable as an adverse event while the second model will classify the dependent variable as an adverse event &lt; grade 3.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response rate</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>Investigate whether response rates by DRD versus non-DRD patients are modified by germline or somatic alteration status of DNA repair pathways.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Castration-Resistant Prostate Carcinoma</condition>
  <condition>Metastatic Malignant Neoplasm in the Bone</condition>
  <condition>Metastatic Prostate Carcinoma</condition>
  <condition>Stage IV Prostate Cancer AJCC v8</condition>
  <condition>Stage IVA Prostate Cancer AJCC v8</condition>
  <condition>Stage IVB Prostate Cancer AJCC v8</condition>
  <arm_group>
    <arm_group_label>Observational (biospecimen collection)</arm_group_label>
    <description>Patients receive standard of care radium Ra 223 dichloride given by IV bolus every 4 weeks for up to 6 cycles. Patients undergo collection of blood every 1-3 months during radium Ra 223 dichloride treatment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Biospecimen Collection</intervention_name>
    <description>Undergo collection of blood samples</description>
    <arm_group_label>Observational (biospecimen collection)</arm_group_label>
    <other_name>Biological Sample Collection</other_name>
    <other_name>Biospecimen Collected</other_name>
    <other_name>Specimen Collection</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Questionnaire Administration</intervention_name>
    <description>Ancillary studies</description>
    <arm_group_label>Observational (biospecimen collection)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Radium Ra 223 Dichloride</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Observational (biospecimen collection)</arm_group_label>
    <other_name>Alpharadin</other_name>
    <other_name>BAY 88-8223</other_name>
    <other_name>BAY88-8223</other_name>
    <other_name>Radium 223 Dichloride</other_name>
    <other_name>RADIUM RA-223 DICHLORIDE</other_name>
    <other_name>Radium-223 Dichloride</other_name>
    <other_name>Xofigo</other_name>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      whole blood&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with mCRPC with bone metastases who are undergoing treatment with radium-223&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient must be &gt;= 18 years of age&#xD;
&#xD;
          -  Patient must have histopathologic diagnosis of prostate cancer&#xD;
&#xD;
          -  Patient must have castration-resistant prostate cancer&#xD;
&#xD;
          -  Patient must have radiographic evidence of bone metastasis&#xD;
&#xD;
          -  Patients must be symptomatic from prostate cancer&#xD;
&#xD;
          -  Patient must have plans to undergo treatment with radium-223&#xD;
&#xD;
          -  Patient must have a PSA level &gt;= 10 ng/mL&#xD;
&#xD;
          -  Patient must have castrate testosterone levels demonstrated within the last 3 months&#xD;
             prior to screening&#xD;
&#xD;
          -  Patient must have anticipated survival &gt; 3 months&#xD;
&#xD;
          -  Patient must be willing and able to authorize consent&#xD;
&#xD;
          -  Patient must be willing and able to comply with the protocol, including follow-up&#xD;
             visits&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient must not have visceral metastasis&#xD;
&#xD;
          -  Patients on regimens of radium-223 in combination with other antineoplastic agents are&#xD;
             excluded&#xD;
&#xD;
             * Bone-targeted only therapy (e.g. denosumab or zoledronic acid) will be allowed&#xD;
&#xD;
          -  Patients who have received prior radium-223&#xD;
&#xD;
          -  Patients who have received prior platinum containing chemotherapy&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &lt; 1.5 x 10^9/L&#xD;
&#xD;
          -  Hemoglobin (HB) &lt; 9 g/dL&#xD;
&#xD;
          -  Platelets (PLT) &lt; 100 x 10^9/L&#xD;
&#xD;
          -  Any condition which, in the investigator's opinion, makes the subject unsuitable for&#xD;
             trial participation&#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>Evan Y. Yu, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fred Hutch/University of Washington Cancer Consortium</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Patrick Panlasigui</last_name>
    <phone>206-606-7486</phone>
    <email>ppanlas2@seattlecca.org</email>
  </overall_contact>
  <location>
    <facility>
      <name>Johns Hopkins University</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Noura Radwan</last_name>
      <phone>410-614-1570</phone>
      <email>Nradwan1@jh.edu</email>
    </contact>
    <investigator>
      <last_name>Ana Kiess, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Bozeman Health Deaconess Hospital</name>
      <address>
        <city>Bozeman</city>
        <state>Montana</state>
        <zip>59715</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Fred Hutch/University of Washington Cancer Consortium</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Patrick Panlasigui</last_name>
      <phone>206-606-7486</phone>
      <email>ppanlas2@seattlecca.org</email>
    </contact>
    <investigator>
      <last_name>Evan Y. Yu, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Wisconsin-Madison</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53705</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Glenn Liu, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>July 23, 2020</study_first_submitted>
  <study_first_submitted_qc>July 23, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 28, 2020</study_first_posted>
  <last_update_submitted>August 22, 2023</last_update_submitted>
  <last_update_submitted_qc>August 22, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 24, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Prostate</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Prostatic Neoplasms</mesh_term>
    <mesh_term>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>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04489719
org study id: RG1006011
secondary id: NCI-2020-04699
secondary id: 10370
nct id: NCT04489719
lead sponsor: 
collaborator: 
has dmc: No
This study investigates how well radium-223 works in treating patients with
      castration-resistant prostate cancer than has spread to the bones (bone metastases). Prostate
      cancer is the most common cancer in men and the second leading cause of cancer death.
      Furthermore, many men with notably advanced disease have been found to have abnormalities in
      DNA repair. The purpose of this research is to study the role of a DNA repair pathway in
      prostate cancer, specifically in response to administration of radium-223, an FDA-approved
      drug known to cause DNA damage to cancerous cells. Understanding how defects in the DNA
      repair pathway affects radium-223 treatment of prostate, may help doctors help plan effective
      treatment in future patients.
OUTLINE:

      Patients receive standard of care radium Ra 223 dichloride given by intravenous (IV) bolus
      every 4 weeks for up to 6 cycles. Patients undergo collection of blood every 1-3 months
      during radium Ra 223 dichloride treatment.

      After completion of study, patients are followed up every 3 months for up to 5 years from the
      date of treatment completion.
observational model: Cohort
time perspective: Prospective
measure: Response rate
time frame: Up to 1 year
description: Response will be defined as having one or both of the following: confirmed prostate specific antigen (PSA) decline of >= 30% from baseline AND/OR confirmed alkaline phosphatase (ALP) decline >= 30% from baseline. Response is evaluated throughout the course of treatment until the post-radium-223 end of treatment laboratory studies. Confirmation of response by PSA and/or ALP requires a second consecutive value obtained >= 2 weeks after the first with sustained >= 30% decline. Characterization of response rate to radium-223 in the DRD patient population will be assessed by binomial proportion with Clopper-Pearson exact 2-sided 95% confidence intervals.
measure: Response rate
time frame: Up to 1 year
description: Comparison of treatment response (outcome/dependent variable) between cases and controls will be assessed using multivariate logistic regression modelling adjusting for secondary variables as appropriate. Risk estimates will include odds ratios with 95% confidence intervals.
measure: Response rate in those with previous PARP inhibitor therapy
time frame: Up to 1 year
description: A multivariate logistic model with PARP inhibitor status as a secondary independent variable and a sensitivity analysis excluding those exposed to PARP inhibitors.
measure: Overall survival
time frame: Up to 5 years
description: Survival by DRD status will be illustrated using univariate Kaplan-Meier curves. Additionally, Cox-PH model adjusting for age, Eastern Cooperative Oncology Group (ECOG) performance status, Gleason grade score, baseline ALP, PSA, hemoglobin (HB), and lactate dehydrogenase (LDH) will be performed. This analysis may be limited by expected small number of events, thus it may be limited to raw reporting of events by DRD status.
measure: Number of radium Ra 223 dichloride
time frame: Up to 6 months
measure: Pain assessment
time frame: Up to 1 year
description: Assessed via Brief Pain Inventory survey
measure: Analgesic usage
time frame: Up to 1 year
measure: Quality of life (FACT-P survey)
time frame: Up to 1 year
description: Assessed via FACT-P quality of life survey
measure: Incidence of adverse events
time frame: Up to 1 year
description: To access risk of adverse events by DRD status, 2 logistic models will be used. The first will classify the dependent variable as an adverse event while the second model will classify the dependent variable as an adverse event < grade 3.
measure: Response rate
time frame: Up to 1 year
description: Investigate whether response rates by DRD versus non-DRD patients are modified by germline or somatic alteration status of DNA repair pathways.
arm group label: Observational (biospecimen collection)
description: Patients receive standard of care radium Ra 223 dichloride given by IV bolus every 4 weeks for up to 6 cycles. Patients undergo collection of blood every 1-3 months during radium Ra 223 dichloride treatment.
intervention type: Procedure
intervention name: Biospecimen Collection
description: Undergo collection of blood samples
arm group label: Observational (biospecimen collection)
other name: Biological Sample Collection
other name: Biospecimen Collected
other name: Specimen Collection
intervention type: Other
intervention name: Questionnaire Administration
description: Ancillary studies
arm group label: Observational (biospecimen collection)
intervention type: Drug
intervention name: Radium Ra 223 Dichloride
description: Given IV
arm group label: Observational (biospecimen collection)
other name: Alpharadin
other name: BAY 88-8223
other name: BAY88-8223
other name: Radium 223 Dichloride
other name: RADIUM RA-223 DICHLORIDE
other name: Radium-223 Dichloride
other name: Xofigo
whole blood
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Evan Y. Yu, MD
role: Principal Investigator
affiliation: Fred Hutch/University of Washington Cancer Consortium
last name: Patrick Panlasigui
phone: 206-606-7486
email: ppanlas2@seattlecca.org
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Active, not recruiting
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Prostatic Neoplasms
mesh term: Neoplasms
mesh term: Radium Ra 223 dichloride
sharing ipd: No