<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/NCT02981797</url>
  </required_header>
  <id_info>
    <org_study_id>MCC-17725</org_study_id>
    <secondary_id>ONC-2013-067</secondary_id>
    <nct_id>NCT02981797</nct_id>
  </id_info>
  <brief_title>Assess Gamma H2AX Positivity in Circulating Prostate Cancer Cells Before and After Radium 223</brief_title>
  <official_title>Assess Gamma H2AX Positivity in Circulating Prostate Cancer Cells Before and After Radium 223 Treatment</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>H. Lee Moffitt Cancer Center and Research Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Bayer</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>H. Lee Moffitt Cancer Center and Research Institute</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a prospective biomarker study on prostate cancer patients receiving Radium 223 as&#xD;
      standard of care.&#xD;
&#xD;
      Participants will take part in this research study because they have chosen Radium 223&#xD;
      treatment for their prostate cancer that has spread to the bone and causing pain.&#xD;
      Investigators want to find out if a blood test performed before and after the Radium 223&#xD;
      treatment will help to understand how prostate cancer cells react to this therapy.&#xD;
&#xD;
      In this pilot study, researchers want to find out if Radium 223 given as part of standard&#xD;
      treatment for prostate cancer can decrease the number of circulating prostate cancer cells.&#xD;
      Radium 223 kills prostate cancer cells by damaging their DNA. Other than looking at the&#xD;
      changes in the number of circulating prostate cancer cells before and after Radium 223,&#xD;
      researchers would also like to look at the changes in a DNA damage marker, called gamma H2AX,&#xD;
      in the circulating prostate cancer cells before and after treatment with Radium 223.&#xD;
      Assessing the DNA damage marker gamma H2AX is investigational. It is performed in the same&#xD;
      tube of blood that is used for assessing the changes in the number of circulating prostate&#xD;
      cancer cells.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In this pilot study, researchers want to find out if Radium 223 given as part of standard&#xD;
      treatment for prostate cancer can decrease the number of circulating prostate cancer cells.&#xD;
      Radium 223 kills prostate cancer cells by damaging their DNA. Other than looking at the&#xD;
      changes in the number of circulating prostate cancer cells before and after Radium 223,&#xD;
      researchers would also like to look at the changes in a DNA damage marker, called gamma H2AX,&#xD;
      in the circulating prostate cancer cells before and after treatment with Radium 223.&#xD;
      Assessing the DNA damage marker gamma H2AX is investigational. It is performed in the same&#xD;
      tube of blood that is used for assessing the changes in the number of circulating prostate&#xD;
      cancer cells.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 22, 2015</start_date>
  <completion_date type="Actual">November 5, 2020</completion_date>
  <primary_completion_date type="Actual">August 29, 2017</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in Gamma H2AX Positivity</measure>
    <time_frame>24 weeks per participant</time_frame>
    <description>Assess changes in gamma H2AX positivity in circulating prostate cancer cells before and after Radium 223 treatment. CTC numeration, the gamma-H2AX detection and interpretation will be performed by Veridex with the cell search platform.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in Circulating Prostate Cancer Cell Numbers</measure>
    <time_frame>24 weeks per participant</time_frame>
    <description>Assess changes in circulating prostate cancer cell numbers before and after Radium 223 treatment. CTC numeration, the gamma-H2AX detection and interpretation will be performed by Veridex with the cell search platform.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pain Response</measure>
    <time_frame>Up to 24 weeks</time_frame>
    <description>Pain response based on Brief Pain Inventory. Pain will be assessed using the Brief Pain Inventory (BPI) Items #3 (worst pain over the last 24 hours by recall), #5 (average pain over the past 24 hours by recall) and #9 (interference with daily activities and sleep).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Narcotic Analgesic Use</measure>
    <time_frame>Up to 24 weeks</time_frame>
    <description>Changes in narcotic analgesic use in participants requiring narcotics at baseline at each radium 223 treatment and week 24. Participants will self-report analgesic use over the past 24 hours.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PSA Response</measure>
    <time_frame>At week 12</time_frame>
    <description>PSA response (30% decline of pretreatment PSA) at week 12.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Bone Scan Response</measure>
    <time_frame>Up to 24 weeks</time_frame>
    <description>Bone scan response based on bone scan index at week 12 and week 24 from dose 1 radium 223 treatment compared with baseline. Response based on the prostate cancer work group 2 (PCWG2) criteria will be assessed at week 12 and week 24 from dose 1 radium 223 treatment and compared with the baseline bone scan.</description>
  </other_outcome>
  <other_outcome>
    <measure>Changes in Alkaline Phosphatase</measure>
    <time_frame>Up to 24 weeks</time_frame>
    <description>Changes in alkaline phosphatase at week 12, week 24 compared to baseline.</description>
  </other_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">10</enrollment>
  <condition>Prostate Cancer</condition>
  <condition>Prostate Adenocarcinoma</condition>
  <arm_group>
    <arm_group_label>Radium 223 Standard of Care</arm_group_label>
    <description>Standard of Care and Blood Collection for Baseline Circulating Tumor Cells (CTCs) Numeration and H2AX Assay. Participants who have chosen Radium 223 treatment for their prostate cancer that has spread to the bone and causing pain. Week 1 starts with the first Radium 223 treatment and week 24 ends 4 weeks after the last or sixth Radium 223 treatment. The circulating prostate cancer cell analysis will be performed within 24 hours of blood draw. Any unused blood samples for circulating prostate cancer cell analysis will be disposed per lab protocol.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Blood Collection During Standard of Care Treatment</intervention_name>
    <description>Blood collection for baseline CTC numeration and H2AX assay. Circulating prostate cancer cell analysis requires blood draw of 7.5 ml (about 1 ½ teaspoons) of blood, to be performed at the screening, 1-2 hours before the third and sixth dose of radium 223 and 24 hours after the first, third, sixth dose of Radium 223. Standard of care Radium 223 treatment is given every 4 weeks for a total of 6 treatments and post Radium 223 follow up at week 24 is also considered standard of care. Other than these standard clinic visits and treatments, the study only requires 3 extra trips to the cancer center for blood draw at 24 hours after the first, third, sixth dose of Radium 223. Blood draws other than circulating tumor cell analysis is considered standard of care and doesn't require extra visits.</description>
    <arm_group_label>Radium 223 Standard of Care</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Participants who have chosen Radium 223 treatment as Standard of Care, for their prostate&#xD;
        cancer that has spread to the bone and causing pain.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male patients 18 years or older&#xD;
&#xD;
          -  Histologically or cytologically confirmed adenocarcinoma of the prostate&#xD;
&#xD;
          -  Receiving radium 223 as standard of care for symptomatic metastatic castration&#xD;
             resistant prostate cancer to the bone as documented by bone scan or Sodium Fluoride&#xD;
             positron emission tomography (PET) bone scan.&#xD;
&#xD;
          -  No evidence of visceral metastasis&#xD;
&#xD;
          -  Prior surgical castration or concurrent use of GnRH analogue (i.e., medical&#xD;
             castration) with testosterone at screening &lt;50 ng/dL.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 -2, ECOG 3 is allowed&#xD;
             if due to pain&#xD;
&#xD;
          -  Adequate organ function: Serum alanine aminotransferase (ALT) or aspirate&#xD;
             aminotransferase (AST) must be &lt; 2.5 x upper limit of normal (ULN); Total bilirubin &lt;&#xD;
             1.5 s ULN; Estimated creatinine clearance must be &gt;40 mL/min; Absolute neutrophil&#xD;
             count (ANC) &gt; 1500/l; Hemoglobin above 10 g/dl; platelet count &gt; 100,000/l.&#xD;
&#xD;
          -  Stable medical condition, including the absence of acute exacerbations of chronic&#xD;
             illnesses, serious infections or major surgery within 28 days prior to study&#xD;
             enrollment&#xD;
&#xD;
          -  Life expectancy of 6 months or more&#xD;
&#xD;
          -  Must agree to practice effective barrier contraception during the entire study&#xD;
             treatment period &amp; through for 6 months after the last dose of study drug, or agree to&#xD;
             completely abstain from heterosexual intercourse&#xD;
&#xD;
          -  Able to give written informed consent&#xD;
&#xD;
          -  Have at least 2 CTCs at baseline&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Exposure to radioisotope therapy (samarium 153, strontium 89) within 24 weeks or&#xD;
             exposure to external beam radiation within 12 weeks of receiving the first dose of&#xD;
             Radium 223&#xD;
&#xD;
          -  Documented central nervous system metastases, has a history of seizure, stroke or&#xD;
             transient ischemic attack (TIA)&#xD;
&#xD;
          -  Treatment with any investigational compound within 30 days prior to the first dose of&#xD;
             study drugs&#xD;
&#xD;
          -  Diagnosis or treatment for another systemic malignancy within 2 years before the first&#xD;
             dose of study drugs, or previously diagnosed with another malignancy &amp; have any&#xD;
             evidence of residual disease. Patients with non-melanoma skin cancer or carcinoma in&#xD;
             situ of any type are not excluded if they have undergone complete resection.&#xD;
&#xD;
          -  New York Association Class III or IV heart failure&#xD;
&#xD;
          -  Known human immunodeficiency virus (HIV) infection, active chronic hepatitis B or C,&#xD;
             life threatening illness unrelated to cancer, or any serious medical or psychiatric&#xD;
             illness that could, in investigators opinion, potentially interfere with participation&#xD;
             in this study.&#xD;
&#xD;
          -  Potential participants with delayed healing of wounds, ulcers, and/or bone fractures&#xD;
&#xD;
          -  Inability to comply with protocol requirements&#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>Jingsong Zhang, M.D., Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>H. Lee Moffitt Cancer Center and Research Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>H. Lee Moffitt Cancer Center and Research Institute</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://moffitt.org/clinical-trials-research/</url>
    <description>Moffitt Cancer Center Clinical Trials website</description>
  </link>
  <verification_date>June 2021</verification_date>
  <study_first_submitted>November 29, 2016</study_first_submitted>
  <study_first_submitted_qc>December 1, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 5, 2016</study_first_posted>
  <last_update_submitted>June 10, 2021</last_update_submitted>
  <last_update_submitted_qc>June 10, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 11, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>symptomatic bone metastasis</keyword>
  <keyword>metastatic</keyword>
  <keyword>castration resistant</keyword>
  <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/NCT02981797
org study id: MCC-17725
secondary id: ONC-2013-067
nct id: NCT02981797
lead sponsor: 
collaborator: 
has dmc: No
This is a prospective biomarker study on prostate cancer patients receiving Radium 223 as
      standard of care.

      Participants will take part in this research study because they have chosen Radium 223
      treatment for their prostate cancer that has spread to the bone and causing pain.
      Investigators want to find out if a blood test performed before and after the Radium 223
      treatment will help to understand how prostate cancer cells react to this therapy.

      In this pilot study, researchers want to find out if Radium 223 given as part of standard
      treatment for prostate cancer can decrease the number of circulating prostate cancer cells.
      Radium 223 kills prostate cancer cells by damaging their DNA. Other than looking at the
      changes in the number of circulating prostate cancer cells before and after Radium 223,
      researchers would also like to look at the changes in a DNA damage marker, called gamma H2AX,
      in the circulating prostate cancer cells before and after treatment with Radium 223.
      Assessing the DNA damage marker gamma H2AX is investigational. It is performed in the same
      tube of blood that is used for assessing the changes in the number of circulating prostate
      cancer cells.
In this pilot study, researchers want to find out if Radium 223 given as part of standard
      treatment for prostate cancer can decrease the number of circulating prostate cancer cells.
      Radium 223 kills prostate cancer cells by damaging their DNA. Other than looking at the
      changes in the number of circulating prostate cancer cells before and after Radium 223,
      researchers would also like to look at the changes in a DNA damage marker, called gamma H2AX,
      in the circulating prostate cancer cells before and after treatment with Radium 223.
      Assessing the DNA damage marker gamma H2AX is investigational. It is performed in the same
      tube of blood that is used for assessing the changes in the number of circulating prostate
      cancer cells.
observational model: Case-Only
time perspective: Prospective
measure: Changes in Gamma H2AX Positivity
time frame: 24 weeks per participant
description: Assess changes in gamma H2AX positivity in circulating prostate cancer cells before and after Radium 223 treatment. CTC numeration, the gamma-H2AX detection and interpretation will be performed by Veridex with the cell search platform.
measure: Changes in Circulating Prostate Cancer Cell Numbers
time frame: 24 weeks per participant
description: Assess changes in circulating prostate cancer cell numbers before and after Radium 223 treatment. CTC numeration, the gamma-H2AX detection and interpretation will be performed by Veridex with the cell search platform.
measure: Pain Response
time frame: Up to 24 weeks
description: Pain response based on Brief Pain Inventory. Pain will be assessed using the Brief Pain Inventory (BPI) Items #3 (worst pain over the last 24 hours by recall), #5 (average pain over the past 24 hours by recall) and #9 (interference with daily activities and sleep).
measure: Changes in Narcotic Analgesic Use
time frame: Up to 24 weeks
description: Changes in narcotic analgesic use in participants requiring narcotics at baseline at each radium 223 treatment and week 24. Participants will self-report analgesic use over the past 24 hours.
measure: PSA Response
time frame: At week 12
description: PSA response (30% decline of pretreatment PSA) at week 12.
measure: Bone Scan Response
time frame: Up to 24 weeks
description: Bone scan response based on bone scan index at week 12 and week 24 from dose 1 radium 223 treatment compared with baseline. Response based on the prostate cancer work group 2 (PCWG2) criteria will be assessed at week 12 and week 24 from dose 1 radium 223 treatment and compared with the baseline bone scan.
measure: Changes in Alkaline Phosphatase
time frame: Up to 24 weeks
description: Changes in alkaline phosphatase at week 12, week 24 compared to baseline.
arm group label: Radium 223 Standard of Care
description: Standard of Care and Blood Collection for Baseline Circulating Tumor Cells (CTCs) Numeration and H2AX Assay. Participants who have chosen Radium 223 treatment for their prostate cancer that has spread to the bone and causing pain. Week 1 starts with the first Radium 223 treatment and week 24 ends 4 weeks after the last or sixth Radium 223 treatment. The circulating prostate cancer cell analysis will be performed within 24 hours of blood draw. Any unused blood samples for circulating prostate cancer cell analysis will be disposed per lab protocol.
intervention type: Other
intervention name: Blood Collection During Standard of Care Treatment
description: Blood collection for baseline CTC numeration and H2AX assay. Circulating prostate cancer cell analysis requires blood draw of 7.5 ml (about 1 ½ teaspoons) of blood, to be performed at the screening, 1-2 hours before the third and sixth dose of radium 223 and 24 hours after the first, third, sixth dose of Radium 223. Standard of care Radium 223 treatment is given every 4 weeks for a total of 6 treatments and post Radium 223 follow up at week 24 is also considered standard of care. Other than these standard clinic visits and treatments, the study only requires 3 extra trips to the cancer center for blood draw at 24 hours after the first, third, sixth dose of Radium 223. Blood draws other than circulating tumor cell analysis is considered standard of care and doesn't require extra visits.
arm group label: Radium 223 Standard of Care
study pop: 
sampling method: Probability Sample
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jingsong Zhang, M.D., Ph.D.
role: Principal Investigator
affiliation: H. Lee Moffitt Cancer Center and Research Institute
facility: 
country: United States
url: https://moffitt.org/clinical-trials-research/
description: Moffitt Cancer Center Clinical Trials website
responsible party type: Sponsor
mesh term: Prostatic Neoplasms