xml: <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/NCT06016699</url>
    </required_header>
    <id_info>
      <org_study_id>NL75013.042.20</org_study_id>
      <nct_id>NCT06016699</nct_id>
    </id_info>
    <brief_title>Immunological Function After Radiation With Either Proton or Photon Therapy</brief_title>
    <acronym>PRO-IMMUNO</acronym>
    <official_title>Effect of Protons Versus Photons on Immunological Function in Head and Neck Cancer: a Pilot Study</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University Medical Center Groningen</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>University Medical Center Groningen</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>
        This is a pilot prospective observational cohort study, comprising patients with head and&#xD;
        neck cancer (HNSCC) treated with standard of care definitive (chemo)radiation either with&#xD;
        photons or protons. Patients will be assigned for protons or photons based on the guidelines&#xD;
        of the National Indication Protocol for Proton therapy of the Netherlands.&#xD;
  &#xD;
        Immunological function will be evaluated by the collection of peripheral blood mononuclear&#xD;
        cells (PBMCs). Blood samples will be collected at baseline, during (chemo)radiation (end of&#xD;
        week 3 and/or before week 4 of treatment) and after completion of (chemo)radiation (week 9,&#xD;
        week 12, week 20, week 34 and week 60, respectively 1 week, 5 weeks, 3 months, 6 months and&#xD;
        12 months after completion of (chemo)radiation). To quantify immunological function, PBMCs&#xD;
        collected during (chemo)radiation and after (chemo)radiation will be compared with that&#xD;
        before (chemo)radiation (week 0), using IFN-γ-ELISPOT to screen for the presence of&#xD;
        antigen-specific T-cell responses. Furthermore, flow cytometry panels will be used to&#xD;
        determine global changes in immune cell proficiency.&#xD;
  &#xD;
        Histological evaluation will take place at baseline and week 3 to examine changes in immune&#xD;
        infiltration within tumour tissue during proton versus photon (chemo)radiation. This biopsy&#xD;
        part of the study is optional for the patient. Archival tissue from the biopsy that was taken&#xD;
        at diagnosis will be used for the baseline assessments. Biopsy at week 3 week will be taken&#xD;
        for all patients who agree to participate in this optional part of the study.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">September 23, 2021</start_date>
    <completion_date type="Anticipated">April 1, 2024</completion_date>
    <primary_completion_date type="Anticipated">April 1, 2024</primary_completion_date>
    <study_type>Observational [Patient Registry]</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>
    <target_duration>12 Months</target_duration>
    <primary_outcome>
      <measure>The difference in antigen-specific immunity in HNSCC patients undergoing (chemo)radiation with protons versus photons.</measure>
      <time_frame>At baseline (week 0), during (chemo)radiation (week 3) and after (chemo)radiation (week 9, week 12, week 20, week 34 and week 60, respectively week, 5 weeks, 3 months, 6 months and 12 months after completion of (chemo)radiation)</time_frame>
      <description>Antigen-specific immunity will be assessed by monitoring antigen-specific T-cell responses in peripheral blood before, during and after (chemo)radiation (up to 12 months after completion of (chemo)radiation) to viral peptides such as SARS-CoV-2 peptides and CEF peptides (CMV, EBV and Influenza).</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Differences in composition and function of circulating immune cells during and after (chemo)radiation with protons versus photons.</measure>
      <time_frame>At baseline (week 0), during (chemo)radiation (week 3) and after (chemo)radiation (week 9, week 12, week 20, week 34 and week 60, respectively week, 5 weeks, 3 months, 6 months and 12 months after completion of (chemo)radiation)</time_frame>
      <description>Differences in composition and function of circulating immune cells will be determined by flow cytometry-based assays using marker for e.g. T- and B-lymphocytes and different myeloid cells such as derived suppressor cells.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Immune infiltrate composition within the primary tumour tissue before and during (chemo)radiation with photons versus protons (optional part of the study).</measure>
      <time_frame>At baseline (week 0) and during (chemo)radiation (week 3)</time_frame>
      <description>Immunohistological staining will be performed on these tumour tissues to assess changes in the composition of immune cells after (chemo)radiation with protons versus photons These assays include molecular analyses and immunohistochemical staining to characterize the type of the intratumoral immune cell infiltrate. In particular, immunohistochemical staining to identify immune cell populations and T cell subpopulations within the tumour tissue can be applied, including, but not limited to, CD4, CD8, FoxP3, CD20, CD163, CD68, PDL1 and PD1. Both changes in absolute numbers and ratios of different immune cell types will be assessed.</description>
    </secondary_outcome>
    <number_of_groups>4</number_of_groups>
    <enrollment type="Anticipated">40</enrollment>
    <condition>HNSCC</condition>
    <condition>Head and Neck Cancer</condition>
    <condition>Oropharynx Cancer</condition>
    <condition>Hypopharynx Cancer</condition>
    <condition>Larynx Cancer</condition>
    <arm_group>
      <arm_group_label>Chemoradiation with protons</arm_group_label>
      <description>HNSCC patients treated with standard-of-care chemoradiation with protons.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Chemoradiation with photons</arm_group_label>
      <description>HNSCC patients treated with standard-of-care chemoradiation with photons.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Radiation with protons</arm_group_label>
      <description>HNSCC patients treated with standard-of-care radiation with protons.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Radiation with photons</arm_group_label>
      <description>HNSCC patients treated with standard-of-care radiation with photons.</description>
    </arm_group>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>blood draws</intervention_name>
      <description>Blood draws to collect PBMCs at baseline (week 0), during (chemo)radiation treatment (end of week 3 and/or before delivery of cycle 4 of cisplatin) and after conclusion of (chemo)radiation (week 9, week 12, week 20, week 34 and week 60, respectively 1 week, 5 weeks, 3 months, 6 months and 12 months after completion of (chemo)radiation) in order to compare immunological function upon treatment with either protons or photons</description>
      <arm_group_label>Chemoradiation with photons</arm_group_label>
      <arm_group_label>Chemoradiation with protons</arm_group_label>
      <arm_group_label>Radiation with photons</arm_group_label>
      <arm_group_label>Radiation with protons</arm_group_label>
    </intervention>
    <eligibility>
      <study_pop>
        <textblock>
          The study population will be recruited at the Univeristy Medical Center Groningen (UMCG(&#xD;
          and consists of adult patients recently diagnosed with stage III-IV HNSCC. Both photon and&#xD;
          proton radiation are standard-of-care treatments for patients with HNSCC.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Newly diagnosed stage III-IV HNSCC of the oral cavity, oropharynx, hypopharynx or&#xD;
               larynx.&#xD;
  &#xD;
            -  Treatment with definitive (chemo)radiation (70 Gy with or without weekly cisplatin)&#xD;
               with photons or protons.&#xD;
  &#xD;
            -  Age of 18 years and older.&#xD;
  &#xD;
            -  Elective or therapeutic bilateral neck irradiation indicated.&#xD;
  &#xD;
            -  Written informed consent according to local guidelines.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Unilateral radiotherapy of the neck.&#xD;
  &#xD;
            -  (Diagnostic) resection of the primary tumour.&#xD;
  &#xD;
            -  Chemoradiation with carboplatin and 5-FU or radiation combined with cetuximab.&#xD;
  &#xD;
            -  History of an autoimmune disease or other systemic intercurrent disease that might&#xD;
               affect the immunocompetence of the patient, or current or prior use (4 weeks before&#xD;
               start of the trial) of high dose immunosuppressive therapy.&#xD;
  &#xD;
            -  Additional malignancy that is progressing or has required active treatment within the&#xD;
               past 3 years. Note: participants with basal cell carcinoma of the skin, squamous cell&#xD;
               carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in&#xD;
               situ) that have undergone potentially curative therapy are not excluded.&#xD;
  &#xD;
            -  Participation in a study of an investigational agent or has used an investigational&#xD;
               device within 4 weeks prior enrolment in this trial. Note: participants who have&#xD;
               entered the follow-up phase of an investigational study may participate as long as it&#xD;
               has been 4 weeks after the last dose of the previous investigational agent.&#xD;
  &#xD;
            -  Active infection requiring systemic therapy.&#xD;
  &#xD;
            -  Current pregnancy.&#xD;
  &#xD;
            -  History or current evidence of any condition, therapy or laboratory abnormality that&#xD;
               might confound the results of this trial, interfere with the subject's participation&#xD;
               for the full duration of this trial, or is not in the best interest of the subject to&#xD;
               participate, in the opinion of the treating investigator.&#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_contact>
      <last_name>Tineke Meijer, MD, PhD</last_name>
      <phone>0015 361 6161</phone>
      <email>t.van.zon@umcg.nl</email>
    </overall_contact>
    <location>
      <facility>
        <name>University Medical Center Groningen (UMCG)</name>
        <address>
          <city>Groningen</city>
          <zip>9700 RB</zip>
          <country>Netherlands</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Anneke Eerkens, MSc</last_name>
        <phone>0015 361 6161</phone>
        <email>a.l.eerkens@umcg.nl</email>
      </contact>
    </location>
    <location_countries>
      <country>Netherlands</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 23, 2023</study_first_submitted>
    <study_first_submitted_qc>August 23, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 30, 2023</study_first_posted>
    <last_update_submitted>August 23, 2023</last_update_submitted>
    <last_update_submitted_qc>August 23, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 30, 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>Head and Neck Neoplasms</mesh_term>
      <mesh_term>Oropharyngeal Neoplasms</mesh_term>
      <mesh_term>Laryngeal Neoplasms</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06016699
  org study id: NL75013.042.20
  nct id: NCT06016699
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  This is a pilot prospective observational cohort study, comprising patients with head and
        neck cancer (HNSCC) treated with standard of care definitive (chemo)radiation either with
        photons or protons. Patients will be assigned for protons or photons based on the guidelines
        of the National Indication Protocol for Proton therapy of the Netherlands.
  
        Immunological function will be evaluated by the collection of peripheral blood mononuclear
        cells (PBMCs). Blood samples will be collected at baseline, during (chemo)radiation (end of
        week 3 and/or before week 4 of treatment) and after completion of (chemo)radiation (week 9,
        week 12, week 20, week 34 and week 60, respectively 1 week, 5 weeks, 3 months, 6 months and
        12 months after completion of (chemo)radiation). To quantify immunological function, PBMCs
        collected during (chemo)radiation and after (chemo)radiation will be compared with that
        before (chemo)radiation (week 0), using IFN-γ-ELISPOT to screen for the presence of
        antigen-specific T-cell responses. Furthermore, flow cytometry panels will be used to
        determine global changes in immune cell proficiency.
  
        Histological evaluation will take place at baseline and week 3 to examine changes in immune
        infiltration within tumour tissue during proton versus photon (chemo)radiation. This biopsy
        part of the study is optional for the patient. Archival tissue from the biopsy that was taken
        at diagnosis will be used for the baseline assessments. Biopsy at week 3 week will be taken
        for all patients who agree to participate in this optional part of the study.
  observational model: Cohort
  time perspective: Prospective
  measure: The difference in antigen-specific immunity in HNSCC patients undergoing (chemo)radiation with protons versus photons.
  time frame: At baseline (week 0), during (chemo)radiation (week 3) and after (chemo)radiation (week 9, week 12, week 20, week 34 and week 60, respectively week, 5 weeks, 3 months, 6 months and 12 months after completion of (chemo)radiation)
  description: Antigen-specific immunity will be assessed by monitoring antigen-specific T-cell responses in peripheral blood before, during and after (chemo)radiation (up to 12 months after completion of (chemo)radiation) to viral peptides such as SARS-CoV-2 peptides and CEF peptides (CMV, EBV and Influenza).
  measure: Differences in composition and function of circulating immune cells during and after (chemo)radiation with protons versus photons.
  time frame: At baseline (week 0), during (chemo)radiation (week 3) and after (chemo)radiation (week 9, week 12, week 20, week 34 and week 60, respectively week, 5 weeks, 3 months, 6 months and 12 months after completion of (chemo)radiation)
  description: Differences in composition and function of circulating immune cells will be determined by flow cytometry-based assays using marker for e.g. T- and B-lymphocytes and different myeloid cells such as derived suppressor cells.
  measure: Immune infiltrate composition within the primary tumour tissue before and during (chemo)radiation with photons versus protons (optional part of the study).
  time frame: At baseline (week 0) and during (chemo)radiation (week 3)
  description: Immunohistological staining will be performed on these tumour tissues to assess changes in the composition of immune cells after (chemo)radiation with protons versus photons These assays include molecular analyses and immunohistochemical staining to characterize the type of the intratumoral immune cell infiltrate. In particular, immunohistochemical staining to identify immune cell populations and T cell subpopulations within the tumour tissue can be applied, including, but not limited to, CD4, CD8, FoxP3, CD20, CD163, CD68, PDL1 and PD1. Both changes in absolute numbers and ratios of different immune cell types will be assessed.
  arm group label: Chemoradiation with protons
  description: HNSCC patients treated with standard-of-care chemoradiation with protons.
  arm group label: Chemoradiation with photons
  description: HNSCC patients treated with standard-of-care chemoradiation with photons.
  arm group label: Radiation with protons
  description: HNSCC patients treated with standard-of-care radiation with protons.
  arm group label: Radiation with photons
  description: HNSCC patients treated with standard-of-care radiation with photons.
  intervention type: Other
  intervention name: blood draws
  description: Blood draws to collect PBMCs at baseline (week 0), during (chemo)radiation treatment (end of week 3 and/or before delivery of cycle 4 of cisplatin) and after conclusion of (chemo)radiation (week 9, week 12, week 20, week 34 and week 60, respectively 1 week, 5 weeks, 3 months, 6 months and 12 months after completion of (chemo)radiation) in order to compare immunological function upon treatment with either protons or photons
  arm group label: Chemoradiation with photons
  arm group label: Chemoradiation with protons
  arm group label: Radiation with photons
  arm group label: Radiation with protons
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Tineke Meijer, MD, PhD
  phone: 0015 361 6161
  email: t.van.zon@umcg.nl
  facility: 
  status: Recruiting
  contact: 
  country: Netherlands
  responsible party type: Sponsor
  mesh term: Head and Neck Neoplasms
  mesh term: Oropharyngeal Neoplasms
  mesh term: Laryngeal Neoplasms
  sharing ipd: Undecided