<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/NCT02986867</url>
  </required_header>
  <id_info>
    <org_study_id>STU 092016-055</org_study_id>
    <nct_id>NCT02986867</nct_id>
  </id_info>
  <brief_title>SAbR Induced Innate Immunity in Urothelial Carcinoma, Melanoma, and Cervical Carcinoma</brief_title>
  <official_title>SAbR-Induced Innate Immunity in Urothelial Carcinoma, Melanoma, and Cervical Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Texas Southwestern Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Texas Southwestern Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study is an exploratory prospective, single center study with correlative endpoints. The&#xD;
      study will investigate the association of tumor cGAS STING signaling with SAbR. Tumor core&#xD;
      biopsies will be processed and analyzed as described above. Medical records electronic&#xD;
      medical records will be used to collect demographic and medical information and imaging&#xD;
      studies.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Within 2 weeks of planned SAbR, patients will have a core biopsy of the lesion to receive&#xD;
      SAbR. Laboratory values will be obtained prior to biopsy. Once the laboratory values are&#xD;
      found to be within the safe margin for biopsy, multiple (approximately 5) core biopsies will&#xD;
      be obtained with an 18-guage or 19-gauge needle under CT or US guidance. Tissue will be snap&#xD;
      frozen with liquid nitrogen and immediately transferred to the laboratory of Dr. Zhijian&#xD;
      &quot;James&quot; Chen, PhD, Professor, Department of Molecular Biology.&#xD;
&#xD;
      SAbR will be administered as per the guidelines of UTSW with a single 24-27Gy or three 10-14&#xD;
      Gy/fraction fractions totaling 33-48Gy. Lesions receiving SAbR will be called &quot;radiated&quot;&#xD;
      lesions. Prior irradiated lesions will be excluded. SABR will be administered within 2 weeks&#xD;
      of the study initial core biopsy. The SAbR dose and fractionation scheme is generated to&#xD;
      deliver a potent dose to ablate the targeted lesions and at the same time maximize an immune&#xD;
      response. Since multiple studies have shown an influx of lymphocytes and monocytes after&#xD;
      tumor irradiation and since these cells play a critical role in antigen presentation and&#xD;
      initiation of an adaptive immune response, multiple fraction irradiation which would kill&#xD;
      these infiltrating immunocytes, is discouraged. Therefore a single fraction or a three&#xD;
      fraction treatment regimen is recommended, and a single fraction treatment is preferred over&#xD;
      three fractions. Due to normal organ toxicity and limits of dose constraints, sometimes a&#xD;
      three fraction treatment must be undertaken and in those cases it is recommended that the&#xD;
      treatment course is completed within 7-10 days-preferably 5 business days. Radiation&#xD;
      dose-immune response studies have shown a linear increase in immune response with increased&#xD;
      dose per fraction of radiation without demonstration of a plateau. Two studies comparing 15Gy&#xD;
      x 1 vs 5Gy x3, and 20Gy x1 vs 5Gy x4 have shown a superior immune response generated by the&#xD;
      single fraction radiation. Clinical experience with oligometastatic patients treated at 1-5&#xD;
      sites of disease has also showed an increase in progression-free survival with the increasing&#xD;
      radiation dose per fraction. A dose of less than 7.5 Gy per fraction has demonstrated lower&#xD;
      induction of systemic IFN-γ producing cells, and a previous phase II study of mRCC patients&#xD;
      treated with HD IL-2 and singe fraction of 8Gy irradiation to a single lesion did not show an&#xD;
      overall improvement in response rate. Therefore 8Gy per fraction is the lowest permitted dose&#xD;
      for this study and can be used only when administering the three fraction regimen as&#xD;
      described in the prescription dose table below. Investigators will have discretion in&#xD;
      choosing from either of the biologically equivalent dose levels using one or three fractions,&#xD;
      although a single fraction is preferred over three fraction treatments. Treating physician&#xD;
      will have further discretion in selecting the number and location of sites to treat if&#xD;
      multiple sites of disease are present. Maximum number of lesions treated is deemed as&#xD;
      feasible per the treating radiation oncologist. However, for the purposes of this protocol,&#xD;
      only a single site will be studied and must be safely amenable to repeat core biopsy. Thus,&#xD;
      the single site for the study will be either in subcutaneous tissues, nodes, isolated masses&#xD;
      or liver. The gross target/tumor volume--GTV should be at least 2 cm3 in size, corresponding&#xD;
      to roughly a 1.5 cm diameter tumor. This is to ensure that adequate tumor volume for therapy&#xD;
      and for biopsy and therefore adequate tumor cells roughly 108 -109 cells/cm3 are killed for&#xD;
      antigen presentation. Treating physicians should choose their dose based on established&#xD;
      planning guidelines at their center including their ability to respect normal tissue&#xD;
      tolerance.&#xD;
&#xD;
      Within 24 + 6 hours of the first SAbR, a second core biopsy of the &quot;target&quot; irradiated lesion&#xD;
      will be performed identically to the first biopsy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 13, 2017</start_date>
  <completion_date type="Actual">March 7, 2018</completion_date>
  <primary_completion_date type="Actual">March 7, 2018</primary_completion_date>
  <phase>N/A</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>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Comparison of immune checkpoint treated tumors</measure>
    <time_frame>36 months</time_frame>
    <description>Compare cGAMP levels, interferon response gene expression and phospho-STING in tumors of immune checkpoint treated patients.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>SAbR effects on cGAMP in tumors</measure>
    <time_frame>36 months</time_frame>
    <description>Number of participants with SAbRrelated tumor changes indicated by cGAMP in comparison to Baseline.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>SAbR effects on interferon response in tumors</measure>
    <time_frame>36 months</time_frame>
    <description>Number of participants with SAbRrelated tumor changes indicated by interferon response mRNAs in comparison to Baseline.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>SAbR effects on phosphor-STING in tumors</measure>
    <time_frame>36 months</time_frame>
    <description>Number of participants with SAbRrelated tumor changes indicated by phospho-STING in comparison to Baseline.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">27</enrollment>
  <condition>Urothelial Carcinoma</condition>
  <condition>Melanoma</condition>
  <condition>Cervical Carcinoma in Situ</condition>
  <arm_group>
    <arm_group_label>SAbR</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>SAbR treatment of lesions</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>SAbR Treatment of Lesions</intervention_name>
    <description>SAbR will be administered as per the guidelines of UTSW with a single 24-27Gy or three 10-14 Gy/fraction fractions totaling 33-48Gy. Lesions receiving SAbR will be called &quot;radiated&quot; lesions.</description>
    <arm_group_label>SAbR</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologic diagnosis of advanced/metastatic urothelial carcinoma, melanoma, or&#xD;
             cervical carcinoma.&#xD;
&#xD;
          -  Planned treated with SAbR.&#xD;
&#xD;
          -  Age greater than or equal to 18 years.&#xD;
&#xD;
          -  Lesion to receive SAbR safely accessible for core biopsy-mass &gt;1.5cm diameter and&#xD;
             located in node, liver, or soft tissues.&#xD;
&#xD;
          -  Hgb &gt;10g/dL before or after transfusion.&#xD;
&#xD;
          -  Platelets &gt;50,000/L&#xD;
&#xD;
          -  INR &lt;1.5&#xD;
&#xD;
          -  If contrast enhanced CT needed to locate the lesion for core biopsy, then derived&#xD;
             creatinine clearance &gt;30cc/min&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior radiation therapy to target lesion.&#xD;
&#xD;
          -  Target lesion not safely accessible for core biopsies.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>University of Texas Southwestern Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75063</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>November 21, 2016</study_first_submitted>
  <study_first_submitted_qc>December 5, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 8, 2016</study_first_posted>
  <last_update_submitted>January 8, 2019</last_update_submitted>
  <last_update_submitted_qc>January 8, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 10, 2019</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>Carcinoma</mesh_term>
    <mesh_term>Melanoma</mesh_term>
    <mesh_term>Carcinoma, Transitional Cell</mesh_term>
    <mesh_term>Carcinoma in Situ</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02986867
org study id: STU 092016-055
nct id: NCT02986867
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
The study is an exploratory prospective, single center study with correlative endpoints. The
      study will investigate the association of tumor cGAS STING signaling with SAbR. Tumor core
      biopsies will be processed and analyzed as described above. Medical records electronic
      medical records will be used to collect demographic and medical information and imaging
      studies.
Within 2 weeks of planned SAbR, patients will have a core biopsy of the lesion to receive
      SAbR. Laboratory values will be obtained prior to biopsy. Once the laboratory values are
      found to be within the safe margin for biopsy, multiple (approximately 5) core biopsies will
      be obtained with an 18-guage or 19-gauge needle under CT or US guidance. Tissue will be snap
      frozen with liquid nitrogen and immediately transferred to the laboratory of Dr. Zhijian
      "James" Chen, PhD, Professor, Department of Molecular Biology.

      SAbR will be administered as per the guidelines of UTSW with a single 24-27Gy or three 10-14
      Gy/fraction fractions totaling 33-48Gy. Lesions receiving SAbR will be called "radiated"
      lesions. Prior irradiated lesions will be excluded. SABR will be administered within 2 weeks
      of the study initial core biopsy. The SAbR dose and fractionation scheme is generated to
      deliver a potent dose to ablate the targeted lesions and at the same time maximize an immune
      response. Since multiple studies have shown an influx of lymphocytes and monocytes after
      tumor irradiation and since these cells play a critical role in antigen presentation and
      initiation of an adaptive immune response, multiple fraction irradiation which would kill
      these infiltrating immunocytes, is discouraged. Therefore a single fraction or a three
      fraction treatment regimen is recommended, and a single fraction treatment is preferred over
      three fractions. Due to normal organ toxicity and limits of dose constraints, sometimes a
      three fraction treatment must be undertaken and in those cases it is recommended that the
      treatment course is completed within 7-10 days-preferably 5 business days. Radiation
      dose-immune response studies have shown a linear increase in immune response with increased
      dose per fraction of radiation without demonstration of a plateau. Two studies comparing 15Gy
      x 1 vs 5Gy x3, and 20Gy x1 vs 5Gy x4 have shown a superior immune response generated by the
      single fraction radiation. Clinical experience with oligometastatic patients treated at 1-5
      sites of disease has also showed an increase in progression-free survival with the increasing
      radiation dose per fraction. A dose of less than 7.5 Gy per fraction has demonstrated lower
      induction of systemic IFN-γ producing cells, and a previous phase II study of mRCC patients
      treated with HD IL-2 and singe fraction of 8Gy irradiation to a single lesion did not show an
      overall improvement in response rate. Therefore 8Gy per fraction is the lowest permitted dose
      for this study and can be used only when administering the three fraction regimen as
      described in the prescription dose table below. Investigators will have discretion in
      choosing from either of the biologically equivalent dose levels using one or three fractions,
      although a single fraction is preferred over three fraction treatments. Treating physician
      will have further discretion in selecting the number and location of sites to treat if
      multiple sites of disease are present. Maximum number of lesions treated is deemed as
      feasible per the treating radiation oncologist. However, for the purposes of this protocol,
      only a single site will be studied and must be safely amenable to repeat core biopsy. Thus,
      the single site for the study will be either in subcutaneous tissues, nodes, isolated masses
      or liver. The gross target/tumor volume--GTV should be at least 2 cm3 in size, corresponding
      to roughly a 1.5 cm diameter tumor. This is to ensure that adequate tumor volume for therapy
      and for biopsy and therefore adequate tumor cells roughly 108 -109 cells/cm3 are killed for
      antigen presentation. Treating physicians should choose their dose based on established
      planning guidelines at their center including their ability to respect normal tissue
      tolerance.

      Within 24 + 6 hours of the first SAbR, a second core biopsy of the "target" irradiated lesion
      will be performed identically to the first biopsy.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Comparison of immune checkpoint treated tumors
time frame: 36 months
description: Compare cGAMP levels, interferon response gene expression and phospho-STING in tumors of immune checkpoint treated patients.
measure: SAbR effects on cGAMP in tumors
time frame: 36 months
description: Number of participants with SAbRrelated tumor changes indicated by cGAMP in comparison to Baseline.
measure: SAbR effects on interferon response in tumors
time frame: 36 months
description: Number of participants with SAbRrelated tumor changes indicated by interferon response mRNAs in comparison to Baseline.
measure: SAbR effects on phosphor-STING in tumors
time frame: 36 months
description: Number of participants with SAbRrelated tumor changes indicated by phospho-STING in comparison to Baseline.
arm group label: SAbR
arm group type: Experimental
description: SAbR treatment of lesions
intervention type: Radiation
intervention name: SAbR Treatment of Lesions
description: SAbR will be administered as per the guidelines of UTSW with a single 24-27Gy or three 10-14 Gy/fraction fractions totaling 33-48Gy. Lesions receiving SAbR will be called "radiated" lesions.
arm group label: SAbR
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Melanoma
mesh term: Carcinoma, Transitional Cell
mesh term: Carcinoma in Situ
sharing ipd: No