<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/NCT03258788</url>
  </required_header>
  <id_info>
    <org_study_id>CFTSp095, 14_DOG07_183</org_study_id>
    <nct_id>NCT03258788</nct_id>
  </id_info>
  <brief_title>A Translational Study Investigating PD-L1 Expression After Radiotherapy for Non-small Cell Lung Cancer</brief_title>
  <acronym>PD-RAD</acronym>
  <official_title>A Translational Study Investigating PD-L1 Expression After Radiotherapy for Non-small Cell Lung Cancer (NSCLC)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Christie NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>The Christie NHS Foundation Trust</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Participants with Non-Small Cell Lung Cancer (NSCLC), Performance Status (PS) 0-2, not&#xD;
      suitable for concurrent Chemo-Radiotherapy (CTRT), will be treated with standard radiotherapy&#xD;
      (radical or palliative). Archival tumour biopsies will be analysed for baseline Programmed&#xD;
      Death Ligand 1 (PD-L1) expression. Some participants will have a biopsy before radiotherapy&#xD;
      if the archive biopsy is not suitable. Participants will be required to undergo an additional&#xD;
      mandatory biopsy of the irradiated site during the second week of radiotherapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The purpose of this prospective, multicentre, non-randomised translational study is to&#xD;
      provide proof of feasibility of achieving paired biopsies for PD-L1 assessment in patients&#xD;
      with NSCLC treated with palliative or radical radiotherapy. This is a non-CTIMP study.&#xD;
&#xD;
      All participants will have a minimum of 1 mandatory biopsy (during radiotherapy [irradiated&#xD;
      site]) and the potential to have a pre-treatment biopsy if archival biopsy does not meet the&#xD;
      suitability criteria.&#xD;
&#xD;
      Participants will have up to a maximum of 2 additional optional biopsies (during radiotherapy&#xD;
      [within the RT field e.g supraclavicular fossa node], [outside RT field e.g. skin met]).&#xD;
&#xD;
      Blood samples will also be taken on study at specified time points for immune monitoring&#xD;
      (exploratory endpoints).&#xD;
&#xD;
      The study will be carried out in two stages as follows:&#xD;
&#xD;
      Stage 1:&#xD;
&#xD;
      Following the enrolment of the first 15 evaluable participants, an interim analysis will take&#xD;
      place by the Trial Steering Committee (TSC). The TSC will make a recommendation on whether&#xD;
      recruitment should continue to the Trial Management Group (TMG).&#xD;
&#xD;
      Stage 2:&#xD;
&#xD;
      A further 15 evaluable participants will be recruited onto the study to achieve a total of 30&#xD;
      evaluable participants.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 3, 2019</start_date>
  <completion_date type="Actual">March 18, 2020</completion_date>
  <primary_completion_date type="Actual">March 18, 2020</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>Achieving paired biopsies for PD-L1 assessment in 21 of the 30 evaluable participants</measure>
    <time_frame>Up to 6.5 weeks from start of radiotherapy</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Suitability of pre and during radiotherapy biopsy for PD-L1 testing</measure>
    <time_frame>Up to 6.5 weeks from start of radiotherapy</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Change in PD-L1 expression level during treatment</measure>
    <time_frame>Up to 6.5 weeks from start of radiotherapy</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Difference in PD-L1 expression level in 'out of radiotherapy field' sites compared with irradiated sites</measure>
    <time_frame>Up to 6.5 weeks from start of radiotherapy</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Immune monitoring of primary tumour and peripheral blood mononuclear cells</measure>
    <time_frame>Up to 6.5 weeks from start of radiotherapy</time_frame>
  </other_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">15</enrollment>
  <condition>Non-Small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Non-Small Cell Lung Cancer</arm_group_label>
    <description>Participants with NSCLC not suitable for concurrent CTRT, being treated with standard radiotherapy (radical or palliative). All participants will be required to undergo a post radiotherapy course biopsy and will have blood samples taken.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Biopsy and blood samples</intervention_name>
    <description>Archival tumour biopsies will be analysed for baseline PD-L1 expression. Some participants will have a biopsy before radiotherapy if the archival biopsy is not suitable.&#xD;
Participants will be required to undergo an additional mandatory biopsy of the irradiated site during the second week. Patients must have completed at least 1 week of the planned treatment before taking the biopsy.&#xD;
Participants will also be asked for consent to donate 50ml blood pre biopsy (at baseline and week 2) and at the end of radiotherapy; as well as 10ml blood before #2 radiotherapy and weekly throughout treatment.</description>
    <arm_group_label>Non-Small Cell Lung Cancer</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Original diagnostic tumour blocks will be returned at the end of the study. New biopsy and&#xD;
      blood samples taken may be used in future research.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Hospital clinic&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically confirmed NSCLC&#xD;
&#xD;
          -  Diagnostic/pre-treatment biopsy suitable for PD-L1 analysis*&#xD;
&#xD;
          -  Tumour judged inoperable by a lung MDT&#xD;
&#xD;
          -  Tumour that is accessible to core biopsy&#xD;
&#xD;
          -  Age 18 and over, no upper age limit&#xD;
&#xD;
          -  Performance status (PS) - ECOG 0-2&#xD;
&#xD;
          -  Participant considered suitable for radiotherapy (palliative or radical) or sequential&#xD;
             chemo-radiotherapy&#xD;
&#xD;
          -  Before participant registration, written informed consent must be given according to&#xD;
             GCP and national regulations&#xD;
&#xD;
               -  Pre-treatment biopsy must be from gross tumour volume within planned radiation&#xD;
                  field, and must also:&#xD;
&#xD;
                    -  have been formalin fixed for &gt;12h and ≤24h&#xD;
&#xD;
                    -  have tumour tissue and morphology confirmed by H&amp;E staining&#xD;
&#xD;
                    -  contain sufficient tumour cells (&gt;100) to determine PD-L1 status&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participant suitable for standard concurrent CTRT&#xD;
&#xD;
          -  Participant deemed unsuitable for repeat biopsies in the opinion of the treating&#xD;
             oncologist&#xD;
&#xD;
          -  Participant known to have an EGFR mutation or an ALK rearrangement&#xD;
&#xD;
          -  Intercurrent or history of hepatitis B, C or human immunodeficiency virus infection,&#xD;
             if known&#xD;
&#xD;
          -  Participants who have received more than 1 line of chemotherapy prior to radiotherapy&#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>Timothy Illidge</last_name>
    <role>Study Chair</role>
    <affiliation>The Christie NHS Foundation Trust</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>St. James's Univerisity Hospital</name>
      <address>
        <city>Leeds</city>
        <zip>LS9 7TF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University College Hospital</name>
      <address>
        <city>London</city>
        <zip>NW1 2BU</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Christie NHS Foundation Trust</name>
      <address>
        <city>Manchester</city>
        <zip>M20 4BX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <link>
    <url>https://www.hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/pd-rad/</url>
    <description>End of Trial Report - HRA</description>
  </link>
  <link>
    <url>https://research.manchester.ac.uk/en/publications/pd-rad-a-translational-study-investigating-pd-l1-expression-after</url>
    <description>University of Manchester - Website</description>
  </link>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>August 10, 2017</study_first_submitted>
  <study_first_submitted_qc>August 22, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 23, 2017</study_first_posted>
  <last_update_submitted>March 30, 2023</last_update_submitted>
  <last_update_submitted_qc>March 30, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 3, 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>Lung Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Non-Small-Cell Lung</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/NCT03258788
org study id: CFTSp095, 14_DOG07_183
nct id: NCT03258788
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
Participants with Non-Small Cell Lung Cancer (NSCLC), Performance Status (PS) 0-2, not
      suitable for concurrent Chemo-Radiotherapy (CTRT), will be treated with standard radiotherapy
      (radical or palliative). Archival tumour biopsies will be analysed for baseline Programmed
      Death Ligand 1 (PD-L1) expression. Some participants will have a biopsy before radiotherapy
      if the archive biopsy is not suitable. Participants will be required to undergo an additional
      mandatory biopsy of the irradiated site during the second week of radiotherapy.
The purpose of this prospective, multicentre, non-randomised translational study is to
      provide proof of feasibility of achieving paired biopsies for PD-L1 assessment in patients
      with NSCLC treated with palliative or radical radiotherapy. This is a non-CTIMP study.

      All participants will have a minimum of 1 mandatory biopsy (during radiotherapy [irradiated
      site]) and the potential to have a pre-treatment biopsy if archival biopsy does not meet the
      suitability criteria.

      Participants will have up to a maximum of 2 additional optional biopsies (during radiotherapy
      [within the RT field e.g supraclavicular fossa node], [outside RT field e.g. skin met]).

      Blood samples will also be taken on study at specified time points for immune monitoring
      (exploratory endpoints).

      The study will be carried out in two stages as follows:

      Stage 1:

      Following the enrolment of the first 15 evaluable participants, an interim analysis will take
      place by the Trial Steering Committee (TSC). The TSC will make a recommendation on whether
      recruitment should continue to the Trial Management Group (TMG).

      Stage 2:

      A further 15 evaluable participants will be recruited onto the study to achieve a total of 30
      evaluable participants.
observational model: Cohort
time perspective: Prospective
measure: Achieving paired biopsies for PD-L1 assessment in 21 of the 30 evaluable participants
time frame: Up to 6.5 weeks from start of radiotherapy
measure: Suitability of pre and during radiotherapy biopsy for PD-L1 testing
time frame: Up to 6.5 weeks from start of radiotherapy
measure: Change in PD-L1 expression level during treatment
time frame: Up to 6.5 weeks from start of radiotherapy
measure: Difference in PD-L1 expression level in 'out of radiotherapy field' sites compared with irradiated sites
time frame: Up to 6.5 weeks from start of radiotherapy
measure: Immune monitoring of primary tumour and peripheral blood mononuclear cells
time frame: Up to 6.5 weeks from start of radiotherapy
arm group label: Non-Small Cell Lung Cancer
description: Participants with NSCLC not suitable for concurrent CTRT, being treated with standard radiotherapy (radical or palliative). All participants will be required to undergo a post radiotherapy course biopsy and will have blood samples taken.
intervention type: Procedure
intervention name: Biopsy and blood samples
description: Archival tumour biopsies will be analysed for baseline PD-L1 expression. Some participants will have a biopsy before radiotherapy if the archival biopsy is not suitable.
Participants will be required to undergo an additional mandatory biopsy of the irradiated site during the second week. Patients must have completed at least 1 week of the planned treatment before taking the biopsy.
Participants will also be asked for consent to donate 50ml blood pre biopsy (at baseline and week 2) and at the end of radiotherapy; as well as 10ml blood before #2 radiotherapy and weekly throughout treatment.
arm group label: Non-Small Cell Lung Cancer
Original diagnostic tumour blocks will be returned at the end of the study. New biopsy and
      blood samples taken may be used in future research.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Timothy Illidge
role: Study Chair
affiliation: The Christie NHS Foundation Trust
facility: 
facility: 
facility: 
country: United Kingdom
url: https://www.hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/pd-rad/
description: End of Trial Report - HRA
url: https://research.manchester.ac.uk/en/publications/pd-rad-a-translational-study-investigating-pd-l1-expression-after
description: University of Manchester - Website
responsible party type: Sponsor
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung