<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/NCT03809377</url>
  </required_header>
  <id_info>
    <org_study_id>IRAS258792</org_study_id>
    <nct_id>NCT03809377</nct_id>
  </id_info>
  <brief_title>Transcriptional Responses as an Indicator of Individualised Responses to Radiation Effects (RTGene 2)</brief_title>
  <official_title>Multi-panel Coding and Non-coding Transcriptional Responses as an Indicator of Individualised Responses to Radiation Effects in Radiation Therapy Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institute of Cancer Research, United Kingdom</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Public Health England</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Institute of Cancer Research, United Kingdom</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Peripheral blood samples will be taken with informed consent from radiotherapy patients&#xD;
      before and during treatment fractions for sarcoma, breast, lung, gut, genitourinary and head&#xD;
      &amp; neck tumours at The Royal Marsden. Candidate genes identified by PHE, Columbia and/or in&#xD;
      the literature as being specific to radiation responses will be assessed, together with genes&#xD;
      relevant to systemic inflammatory and immune responses, to identify transcriptional responses&#xD;
      for a range of doses and exposures on an inter-individual basis. Data will be analysed using&#xD;
      existing and new statistical tools focused on count data modelling. The intended outcome is&#xD;
      identification of a radiation specific panel of genes to inform individual radiation&#xD;
      responses and if the results are favourable, a large scale follow up to this project is&#xD;
      expected.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Biomarkers of radiation exposure are recognised to form an important component of the&#xD;
      'toolkit' for initial triage assessment of potentially exposed individuals in a mass casualty&#xD;
      radiation accident or incident. Furthermore, radiation is an important medical tool and&#xD;
      biomarkers can contribute to longer term assessment of radiation effects and public health&#xD;
      risks. The gene expression assay has been gaining popularity as a sensitive biological marker&#xD;
      of radiation exposure with the potential to be used for truly individualised dosimetry. The&#xD;
      possibility for this assay to be used for a large scale mass-casualty scenario has been&#xD;
      proposed and tested in a recent inter-comparison exercise. However, a fuller understanding of&#xD;
      genetic factors that contribute to individual radiation risks is needed to inform tailored&#xD;
      screening approaches - i.e. to identify a truly radiation specific panel of genetics&#xD;
      responses for use as a transcriptional biomarker.&#xD;
&#xD;
      At Columbia University, research has shown that transcriptional effects have the potential to&#xD;
      be used as individualised predictors of radiosensitivity to early and late effects. At Public&#xD;
      Health England (PHE), recently established molecular counting nCounter technology allows&#xD;
      direct counting of nucleic acid molecules (DNA, mRNA, miRNA and lncRNA) without the need for&#xD;
      enzymatic reaction or amplification steps hence reducing time for data collection. This new&#xD;
      gene expression analysis technique has been assessed for radiation biodosimetry applications&#xD;
      with promising results. Furthermore, gene expression has shown a high degree of promise as a&#xD;
      marker for late effects of radiation, for instance normal tissue reactions following curative&#xD;
      radiotherapy for breast cancer.&#xD;
&#xD;
      In the earlier pilot RTGene study the investigators found genes that are consistently&#xD;
      down-regulated and up-regulated towards the end of the radiotherapy treatment. The next stage&#xD;
      of this work (RTGene 2) will be to validate the nCounter data for a small number of new genes&#xD;
      consistently found in the top 6 of differentially expressed. Importantly, in an attempt to&#xD;
      identify genes which are promising biomarkers of susceptibility to radiation-induced&#xD;
      toxicity, expression levels will need to be compared with normal tissue reaction to IR, and&#xD;
      combined with longer term radiation toxicity data to identify genes with the most pronounced&#xD;
      expression level fluctuations during and after radiotherapy.&#xD;
&#xD;
      Peripheral blood samples will be taken with informed consent from radiotherapy patients&#xD;
      before and during treatment fractions for sarcoma, breast, lung, gut, genitourinary and head&#xD;
      &amp; neck tumours at The Royal Marsden. Candidate genes identified by PHE, Columbia and/or in&#xD;
      the literature as being specific to radiation responses will be assessed, together with genes&#xD;
      relevant to systemic inflammatory and immune responses, to identify transcriptional responses&#xD;
      for a range of doses and exposures on an inter-individual basis. Data will be analysed using&#xD;
      existing and new statistical tools focused on count data modelling. The intended outcome is&#xD;
      identification of a radiation specific panel of genes to inform individual radiation&#xD;
      responses and if the results are favourable, a large scale follow up to this project is&#xD;
      expected.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">May 9, 2019</start_date>
  <completion_date type="Anticipated">June 1, 2024</completion_date>
  <primary_completion_date type="Anticipated">June 1, 2024</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>Validation of new transcriptional techniques</measure>
    <time_frame>24 months after all participants have finished radiotherapy and donated blood samples</time_frame>
    <description>Using nCounter platform to validate biomarkers of individual radiation exposure, in vivo</description>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">25</enrollment>
  <condition>Cancer</condition>
  <arm_group>
    <arm_group_label>Blood donation during radiotherapy</arm_group_label>
    <description>Participants will be asked to donate a blood sample at 5 time points during and after radiotherapy</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Blood donation during radiotherapy</intervention_name>
    <description>Participants will be asked to donate a blood sample at 5 time points during and after radiotherapy</description>
    <arm_group_label>Blood donation during radiotherapy</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients undergoing radiotherapy for cancer&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥18 years&#xD;
&#xD;
          -  Requirement for external beam radiotherapy (large-field RT, over at least 2 weeks) for&#xD;
             sarcoma, breast, lung, gastrointestinal, head &amp; neck or genitourinary tumours&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous radiotherapy&#xD;
&#xD;
          -  Concurrent chemotherapy/biological therapy or chemotherapy/biological therapy&#xD;
             preceding radiotherapy by less than 4 weeks&#xD;
&#xD;
          -  Concurrent hormone therapy or hormone therapy preceding radiotherapy by less than 4&#xD;
             weeks&#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>Navita Somaiah</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Institute of Cancer Research, London, UK</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The Royal Marsden NHS Foundation Trust</name>
      <address>
        <city>Sutton</city>
        <state>Surrey</state>
        <zip>SM2 5PT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>January 14, 2019</study_first_submitted>
  <study_first_submitted_qc>January 17, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 18, 2019</study_first_posted>
  <last_update_submitted>August 15, 2023</last_update_submitted>
  <last_update_submitted_qc>August 15, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 16, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03809377
org study id: IRAS258792
nct id: NCT03809377
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Peripheral blood samples will be taken with informed consent from radiotherapy patients
      before and during treatment fractions for sarcoma, breast, lung, gut, genitourinary and head
      & neck tumours at The Royal Marsden. Candidate genes identified by PHE, Columbia and/or in
      the literature as being specific to radiation responses will be assessed, together with genes
      relevant to systemic inflammatory and immune responses, to identify transcriptional responses
      for a range of doses and exposures on an inter-individual basis. Data will be analysed using
      existing and new statistical tools focused on count data modelling. The intended outcome is
      identification of a radiation specific panel of genes to inform individual radiation
      responses and if the results are favourable, a large scale follow up to this project is
      expected.
Biomarkers of radiation exposure are recognised to form an important component of the
      'toolkit' for initial triage assessment of potentially exposed individuals in a mass casualty
      radiation accident or incident. Furthermore, radiation is an important medical tool and
      biomarkers can contribute to longer term assessment of radiation effects and public health
      risks. The gene expression assay has been gaining popularity as a sensitive biological marker
      of radiation exposure with the potential to be used for truly individualised dosimetry. The
      possibility for this assay to be used for a large scale mass-casualty scenario has been
      proposed and tested in a recent inter-comparison exercise. However, a fuller understanding of
      genetic factors that contribute to individual radiation risks is needed to inform tailored
      screening approaches - i.e. to identify a truly radiation specific panel of genetics
      responses for use as a transcriptional biomarker.

      At Columbia University, research has shown that transcriptional effects have the potential to
      be used as individualised predictors of radiosensitivity to early and late effects. At Public
      Health England (PHE), recently established molecular counting nCounter technology allows
      direct counting of nucleic acid molecules (DNA, mRNA, miRNA and lncRNA) without the need for
      enzymatic reaction or amplification steps hence reducing time for data collection. This new
      gene expression analysis technique has been assessed for radiation biodosimetry applications
      with promising results. Furthermore, gene expression has shown a high degree of promise as a
      marker for late effects of radiation, for instance normal tissue reactions following curative
      radiotherapy for breast cancer.

      In the earlier pilot RTGene study the investigators found genes that are consistently
      down-regulated and up-regulated towards the end of the radiotherapy treatment. The next stage
      of this work (RTGene 2) will be to validate the nCounter data for a small number of new genes
      consistently found in the top 6 of differentially expressed. Importantly, in an attempt to
      identify genes which are promising biomarkers of susceptibility to radiation-induced
      toxicity, expression levels will need to be compared with normal tissue reaction to IR, and
      combined with longer term radiation toxicity data to identify genes with the most pronounced
      expression level fluctuations during and after radiotherapy.

      Peripheral blood samples will be taken with informed consent from radiotherapy patients
      before and during treatment fractions for sarcoma, breast, lung, gut, genitourinary and head
      & neck tumours at The Royal Marsden. Candidate genes identified by PHE, Columbia and/or in
      the literature as being specific to radiation responses will be assessed, together with genes
      relevant to systemic inflammatory and immune responses, to identify transcriptional responses
      for a range of doses and exposures on an inter-individual basis. Data will be analysed using
      existing and new statistical tools focused on count data modelling. The intended outcome is
      identification of a radiation specific panel of genes to inform individual radiation
      responses and if the results are favourable, a large scale follow up to this project is
      expected.
observational model: Cohort
time perspective: Prospective
measure: Validation of new transcriptional techniques
time frame: 24 months after all participants have finished radiotherapy and donated blood samples
description: Using nCounter platform to validate biomarkers of individual radiation exposure, in vivo
arm group label: Blood donation during radiotherapy
description: Participants will be asked to donate a blood sample at 5 time points during and after radiotherapy
intervention type: Procedure
intervention name: Blood donation during radiotherapy
description: Participants will be asked to donate a blood sample at 5 time points during and after radiotherapy
arm group label: Blood donation during radiotherapy
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Navita Somaiah
role: Principal Investigator
affiliation: The Institute of Cancer Research, London, UK
facility: 
country: United Kingdom
responsible party type: Sponsor
sharing ipd: Undecided