<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/NCT03042156</url>
  </required_header>
  <id_info>
    <org_study_id>16-6189</org_study_id>
    <nct_id>NCT03042156</nct_id>
  </id_info>
  <brief_title>Immunotherapy And Palliative Radiotherapy Combined In Patients With Advanced Malignancy</brief_title>
  <official_title>Immunotherapy And Palliative Radiotherapy Combined In Patients With Advanced Malignancy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Health Network, Toronto</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Health Network, Toronto</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Immunotherapy includes a class of medication called checkpoint inhibitors, which are a&#xD;
      relatively new medication therapy for many types of cancer which are metastatic, meaning it&#xD;
      has spread to other parts of the body.Immune therapy medication may be given safely with&#xD;
      radiation treatment, and in rare cases it may even make radiotherapy more effective. When&#xD;
      radiation therapy is given in the &quot;palliative&quot; setting it is given to treat pain/discomfort&#xD;
      and not necessarily shrink or get rid of the tumour. Palliative radiotherapy may be given for&#xD;
      many reasons, but common examples include painful bone or liver tumours, brain metastases, or&#xD;
      symptoms from a chest tumour such as feeling breathless, cough, or bleeding. Palliative&#xD;
      radiotherapy is usually given in smaller amounts and less frequently than other types of&#xD;
      radiation therapy. Because checkpoint inhibitors are relatively new there is not a huge&#xD;
      amount of evidence looking at how patients respond when the treatments are combined, or in&#xD;
      which patients immune therapy may make radiation therapy even more effective. This study is&#xD;
      looking at the way patients who are on or about to start immune therapy and who have been&#xD;
      recommended for palliative radiotherapy, respond to the combination of these two treatments.&#xD;
&#xD;
      The purpose of this study is to describe the treatment outcomes in patients with cancer that&#xD;
      has spread who are managed with a combination of immune therapy medication and radiotherapy.&#xD;
      This research is being done because there is limited information about the outcomes of&#xD;
      combined immune therapy and radiotherapy treatment from a patient's perspective, but also in&#xD;
      terms of which patients may have a better response to combined treatment. In particular, the&#xD;
      study aims to describe how combined treatment affects cancer not only in the area where&#xD;
      radiotherapy is given, but also outside the part of the body that receives radiotherapy&#xD;
      (which is called &quot;abscopal&quot; effect).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 10, 2017</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">December 2023</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>Number of patients showing rates of grade 3 or higher toxicity</measure>
    <time_frame>4 months</time_frame>
    <description>Toxicity and safety data for combined therapy with immunotherapy and palliative RT (documentation that the rates of grade 3 or higher toxicity with combined therapy is &lt; 30%) using patient reported outcomes (symptoms, toxicities, quality of life measures), clinical outcomes (physical examination, and CT imaging results) at baseline, 1 and 3 months post radiotherapy.&#xD;
Only the highest toxicity/per patient will be used for analysis, regardless of the time point of when the information is collected</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>In-field response on imaging and evidence of out of field (abscopal) response.</measure>
    <time_frame>4 months</time_frame>
    <description>Documentation of efficacy using CT imaging at 1 and 3 months post radiotherapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The number of ESAS questionnaires completed with the aid of a caregiver</measure>
    <time_frame>1 year</time_frame>
    <description>Gather information on the efficacy collecting PRO's via in person or phone using questionnaires</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>biomarkers analyses as an indicator of abscopal response</measure>
    <time_frame>4 months</time_frame>
    <description>Optional for consenting patients, done at 1 and 3 months post radiotherapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The number of EQ5D questionnaires completed with the aid of a caregive</measure>
    <time_frame>1 year</time_frame>
    <description>Gather information on the efficacy collecting PRO's via in person or phone using questionnaires</description>
  </secondary_outcome>
  <other_outcome>
    <measure>inflammatory and radiation sensitivity signatures from genotyping using archival tissue</measure>
    <time_frame>1 year</time_frame>
    <description>Optional - from consenting patients (n=10) who already have readily available archival tumour tissue</description>
  </other_outcome>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Palliative</condition>
  <condition>Advanced Cancer</condition>
  <condition>Immunotherapy</condition>
  <condition>Radiation Therapy</condition>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Palliative Radiation Therapy</intervention_name>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with advanced malignancy referred for palliative radiotherapy for symptom control&#xD;
        who are either (a) already on a checkpoint inhibitor or (b) about to start immunotherapy&#xD;
        (including PD1 inhibitors, CTLA4 inhibitors or other novel checkpoint inhibitor agents)&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Adults aged 18 years or older&#xD;
&#xD;
          2. Histologically or cytologically confirmed solid tumor malignancy&#xD;
&#xD;
          3. Advanced disease (locally advanced and/or metastatic)&#xD;
&#xD;
          4. Life expectancy &gt; 3 months&#xD;
&#xD;
          5. Patients planned to receive palliative radiotherapy (including whole liver&#xD;
             radiotherapy)&#xD;
&#xD;
          6. Patients who are already on or about to commence a checkpoint inhibitor&#xD;
&#xD;
          7. Measurable disease according to irRECIST on CT or MRI&#xD;
&#xD;
          8. ECOG performance status 0-2&#xD;
&#xD;
          9. Able to provide informed consent&#xD;
&#xD;
         10. Able to complete telephone/email communication&#xD;
&#xD;
         11. Additional criteria for subset of patients for abscopal analysis (to be done post&#xD;
             hoc):&#xD;
&#xD;
               1. Measurable disease outside irradiated volume&#xD;
&#xD;
               2. Must be on same checkpoint inhibitor/immunotherapy (or same class of checkpoint&#xD;
                  inhibitor) for 3 months prior to radiotherapy and have stable disease or&#xD;
                  oligoprogression in past 3 months&#xD;
&#xD;
               3. Availability of prior biopsy specimen (preferably fresh frozen tissue) for&#xD;
                  research and genotyping&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Medical conditions which may be contraindications to radiotherapy&#xD;
&#xD;
          2. Any medical or non-medical issue that would affect the patient's ability to provide&#xD;
             informed consent for study participation, or would interfere with the patient's&#xD;
             treatment on study.&#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>Princess Margaret Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 2M9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>December 28, 2016</study_first_submitted>
  <study_first_submitted_qc>February 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 3, 2017</study_first_posted>
  <last_update_submitted>May 7, 2023</last_update_submitted>
  <last_update_submitted_qc>May 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 9, 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>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/NCT03042156
org study id: 16-6189
nct id: NCT03042156
lead sponsor: 
has dmc: Yes
Immunotherapy includes a class of medication called checkpoint inhibitors, which are a
      relatively new medication therapy for many types of cancer which are metastatic, meaning it
      has spread to other parts of the body.Immune therapy medication may be given safely with
      radiation treatment, and in rare cases it may even make radiotherapy more effective. When
      radiation therapy is given in the "palliative" setting it is given to treat pain/discomfort
      and not necessarily shrink or get rid of the tumour. Palliative radiotherapy may be given for
      many reasons, but common examples include painful bone or liver tumours, brain metastases, or
      symptoms from a chest tumour such as feeling breathless, cough, or bleeding. Palliative
      radiotherapy is usually given in smaller amounts and less frequently than other types of
      radiation therapy. Because checkpoint inhibitors are relatively new there is not a huge
      amount of evidence looking at how patients respond when the treatments are combined, or in
      which patients immune therapy may make radiation therapy even more effective. This study is
      looking at the way patients who are on or about to start immune therapy and who have been
      recommended for palliative radiotherapy, respond to the combination of these two treatments.

      The purpose of this study is to describe the treatment outcomes in patients with cancer that
      has spread who are managed with a combination of immune therapy medication and radiotherapy.
      This research is being done because there is limited information about the outcomes of
      combined immune therapy and radiotherapy treatment from a patient's perspective, but also in
      terms of which patients may have a better response to combined treatment. In particular, the
      study aims to describe how combined treatment affects cancer not only in the area where
      radiotherapy is given, but also outside the part of the body that receives radiotherapy
      (which is called "abscopal" effect).
observational model: Cohort
time perspective: Prospective
measure: Number of patients showing rates of grade 3 or higher toxicity
time frame: 4 months
description: Toxicity and safety data for combined therapy with immunotherapy and palliative RT (documentation that the rates of grade 3 or higher toxicity with combined therapy is < 30%) using patient reported outcomes (symptoms, toxicities, quality of life measures), clinical outcomes (physical examination, and CT imaging results) at baseline, 1 and 3 months post radiotherapy.
Only the highest toxicity/per patient will be used for analysis, regardless of the time point of when the information is collected
measure: In-field response on imaging and evidence of out of field (abscopal) response.
time frame: 4 months
description: Documentation of efficacy using CT imaging at 1 and 3 months post radiotherapy.
measure: The number of ESAS questionnaires completed with the aid of a caregiver
time frame: 1 year
description: Gather information on the efficacy collecting PRO's via in person or phone using questionnaires
measure: biomarkers analyses as an indicator of abscopal response
time frame: 4 months
description: Optional for consenting patients, done at 1 and 3 months post radiotherapy.
measure: The number of EQ5D questionnaires completed with the aid of a caregive
time frame: 1 year
description: Gather information on the efficacy collecting PRO's via in person or phone using questionnaires
measure: inflammatory and radiation sensitivity signatures from genotyping using archival tissue
time frame: 1 year
description: Optional - from consenting patients (n=10) who already have readily available archival tumour tissue
intervention type: Radiation
intervention name: Palliative Radiation Therapy
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Neoplasms