<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/NCT03035890</url>
  </required_header>
  <id_info>
    <org_study_id>WVU010516</org_study_id>
    <nct_id>NCT03035890</nct_id>
  </id_info>
  <brief_title>Hypofractionated Radiation Therapy to Improve Immunotherapy Response in Non-Small Cell Lung Cancer</brief_title>
  <official_title>Use of Response-Adapted Hypofractionated Radiation Therapy to Potentiate the Systemic Immune Response to Checkpoint Inhibitors in Non-Small Cell Lung Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>West Virginia University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>West Virginia Clinical and Translational Science Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>West Virginia University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study includes the additional use of radiation therapy in combination immunotherapy in&#xD;
      order to determine whether the radiation may improve the response of non-small cell lung&#xD;
      cancer to immunotherapy and to monitor any side effects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Preclinical data suggest that radiation therapy may be uniquely suited to combine with immune&#xD;
      checkpoint inhibitors, since radiation can disrupt a tumor's physical barriers to T-cell&#xD;
      infiltration and augment antigen presentation, thus serving as an &quot;in situ personalized&#xD;
      vaccine&quot; to activate the immune system and potentially enhance the systemic response.&#xD;
&#xD;
      The rationale for this study is to determine the safety and efficacy of combined immune&#xD;
      checkpoint inhibitors and radiation therapy in metastatic non-small cell lung cancer&#xD;
      patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 23, 2017</start_date>
  <completion_date type="Actual">June 30, 2022</completion_date>
  <primary_completion_date type="Actual">June 30, 2022</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Best Overall Response</measure>
    <time_frame>From the start of treatment until disease progression up to 2 years.</time_frame>
    <description>Best overall response rate (complete and partial), measured on follow-up imaging as per immune-related Response Criteria (irRC) approx. every three months taking the smallest measurement recorded.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival</measure>
    <time_frame>From the start of treatment until the date of documented progression or death assessed up to 2 years</time_frame>
    <description>Disease status will be evaluated based on imaging results until progression or death; assessed every three months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>From the start of treatment until the date date of death, or the last follow up date on which the participant was reported alive, assessed up to 2 years</time_frame>
    <description>Amount of time from treatment until death, reported via follow up visit or phone call.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse event evaluation</measure>
    <time_frame>From the time of consent at 3 month intervals until 1 year after treatment has stopped or death</time_frame>
    <description>Adverse event will be recorded and graded based on CTCAE version 4</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life Assessment FACT-L</measure>
    <time_frame>3 month intervals from the start of treatment until progression up to 2 years</time_frame>
    <description>Access change in quality of life scores between visits using the FACT-L score. A difference of 3 points will be considered clinically significant.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life Assessment FACT-Fatigue</measure>
    <time_frame>3 month intervals from the start of treatment until progression up to 2 years</time_frame>
    <description>Access change in quality of life between visits using the FACT- Fatigue scores. A difference of 3 points will be considered clinically significant.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">35</enrollment>
  <condition>Non Small Cell Lung Cancer Metastatic</condition>
  <arm_group>
    <arm_group_label>Radiation Therapy + Immunotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>3-5 fraction course of radiation therapy to target lesion concurrent with an immuno-therapeutic agent</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Radiation</intervention_name>
    <description>Radiation therapy will be administered in 3 or 5 fractions over 3-10 days, at a recommended dose of 8-15 Gy per fraction for 3 total fractions (total dose 24-45 Gy) or 6-10 Gy per fraction for 5 total fractions (total dose 30-50 Gy)</description>
    <arm_group_label>Radiation Therapy + Immunotherapy</arm_group_label>
    <other_name>Hypofractionated Radiation</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Immuno-Therapeutic Agent</intervention_name>
    <description>Immune checkpoint inhibitors that are FDA approved for use in patients with metastatic NSCLC will be acceptable for use concurrently with radiotherapy in this trial. The choice of agents will be at the treating medical oncologist's discretion, and include:&#xD;
Nivolumab 240mg or 3 mg/kg once every 2 weeks (14 day cycle)&#xD;
Pembrolizumab 200mg or 2 mg/kg once every 3 weeks (21 day cycle)&#xD;
Atezolizumab 1200 mg once every 3 weeks (21 day cycle)&#xD;
These agents should be continued per standard of care until either disease progression or unacceptable toxicity.</description>
    <arm_group_label>Radiation Therapy + Immunotherapy</arm_group_label>
    <other_name>Immunotherapy</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Stage IV metastatic Non Small Cell Lung Cancer&#xD;
&#xD;
          -  Measurable disease of at least 1.5 cm in greatest dimension at least 2 non-irradiated&#xD;
             sites (except for lymph nodes, in which the short-axis dimension must be at least&#xD;
             1.5cm). There must be at least 1 visceral organ metastasis outside of the brain.&#xD;
&#xD;
          -  History of prior cytotoxic chemotherapy (with or without concomitant radiation&#xD;
             therapy) with subsequent distant (metastatic) disease relapse, or progression of&#xD;
             disease while on chemotherapy.&#xD;
&#xD;
          -  Participant must be planned to receive (or actively receiving) standard of care&#xD;
             checkpoint inhibitor immune therapy. For those patients actively receiving checkpoint&#xD;
             inhibitor immune therapy the duration of immune therapy at the time of enrollment must&#xD;
             be 4 months or less.&#xD;
&#xD;
          -  Life expectancy greater than 3 months&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Active autoimmune disease, primary immunodeficiency syndrome, HIV/AIDS, or hepatitis B&#xD;
             or C&#xD;
&#xD;
          -  Oral corticosteroid dependency&#xD;
&#xD;
          -  Uncontrolled or untreated active brain metastases/CNS disease&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac&#xD;
             arrhythmia&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Joshua Weir, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>WVUCI - Mary Babb Randolph Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>WVU Cancer Institute - Mary Babb Randolph Cancer Center</name>
      <address>
        <city>Morgantown</city>
        <state>West Virginia</state>
        <zip>26506</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>January 23, 2017</study_first_submitted>
  <study_first_submitted_qc>January 27, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 30, 2017</study_first_posted>
  <last_update_submitted>April 24, 2023</last_update_submitted>
  <last_update_submitted_qc>April 24, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 25, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>NSCLC</keyword>
  <keyword>Lung Cancer</keyword>
  <keyword>Non Small Cell Lung Cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Immunomodulating Agents</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>November 20, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/90/NCT03035890/ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <pending_results>
    <submitted>July 18, 2023</submitted>
    <returned>August 2, 2023</returned>
  </pending_results>
  <!-- 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/NCT03035890
org study id: WVU010516
nct id: NCT03035890
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
This study includes the additional use of radiation therapy in combination immunotherapy in
      order to determine whether the radiation may improve the response of non-small cell lung
      cancer to immunotherapy and to monitor any side effects.
Preclinical data suggest that radiation therapy may be uniquely suited to combine with immune
      checkpoint inhibitors, since radiation can disrupt a tumor's physical barriers to T-cell
      infiltration and augment antigen presentation, thus serving as an "in situ personalized
      vaccine" to activate the immune system and potentially enhance the systemic response.

      The rationale for this study is to determine the safety and efficacy of combined immune
      checkpoint inhibitors and radiation therapy in metastatic non-small cell lung cancer
      patients.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Best Overall Response
time frame: From the start of treatment until disease progression up to 2 years.
description: Best overall response rate (complete and partial), measured on follow-up imaging as per immune-related Response Criteria (irRC) approx. every three months taking the smallest measurement recorded.
measure: Progression Free Survival
time frame: From the start of treatment until the date of documented progression or death assessed up to 2 years
description: Disease status will be evaluated based on imaging results until progression or death; assessed every three months.
measure: Overall Survival
time frame: From the start of treatment until the date date of death, or the last follow up date on which the participant was reported alive, assessed up to 2 years
description: Amount of time from treatment until death, reported via follow up visit or phone call.
measure: Adverse event evaluation
time frame: From the time of consent at 3 month intervals until 1 year after treatment has stopped or death
description: Adverse event will be recorded and graded based on CTCAE version 4
measure: Quality of Life Assessment FACT-L
time frame: 3 month intervals from the start of treatment until progression up to 2 years
description: Access change in quality of life scores between visits using the FACT-L score. A difference of 3 points will be considered clinically significant.
measure: Quality of Life Assessment FACT-Fatigue
time frame: 3 month intervals from the start of treatment until progression up to 2 years
description: Access change in quality of life between visits using the FACT- Fatigue scores. A difference of 3 points will be considered clinically significant.
arm group label: Radiation Therapy + Immunotherapy
arm group type: Experimental
description: 3-5 fraction course of radiation therapy to target lesion concurrent with an immuno-therapeutic agent
intervention type: Radiation
intervention name: Radiation
description: Radiation therapy will be administered in 3 or 5 fractions over 3-10 days, at a recommended dose of 8-15 Gy per fraction for 3 total fractions (total dose 24-45 Gy) or 6-10 Gy per fraction for 5 total fractions (total dose 30-50 Gy)
arm group label: Radiation Therapy + Immunotherapy
other name: Hypofractionated Radiation
intervention type: Drug
intervention name: Immuno-Therapeutic Agent
description: Immune checkpoint inhibitors that are FDA approved for use in patients with metastatic NSCLC will be acceptable for use concurrently with radiotherapy in this trial. The choice of agents will be at the treating medical oncologist's discretion, and include:
Nivolumab 240mg or 3 mg/kg once every 2 weeks (14 day cycle)
Pembrolizumab 200mg or 2 mg/kg once every 3 weeks (21 day cycle)
Atezolizumab 1200 mg once every 3 weeks (21 day cycle)
These agents should be continued per standard of care until either disease progression or unacceptable toxicity.
arm group label: Radiation Therapy + Immunotherapy
other name: Immunotherapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Joshua Weir, MD
role: Principal Investigator
affiliation: WVUCI - Mary Babb Randolph Cancer Center
facility: 
country: United States
responsible party type: Sponsor
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Immunomodulating Agents
sharing ipd: No
provided document: 
submitted: July 18, 2023
returned: August 2, 2023