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/NCT06012604</url>
    </required_header>
    <id_info>
      <org_study_id>ERIDNPVO-0038/2023</org_study_id>
      <nct_id>NCT06012604</nct_id>
    </id_info>
    <brief_title>Treatment of Post-radiation Xerostomia With Allogeneic Mesenchymal Stromal Stem Cells</brief_title>
    <official_title>Treatment of Post-radiation Xerostomia With Allogeneic Mesenchymal Stromal Stem Cells: a Pilot Study</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Institute of Oncology Ljubljana</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Blood Transfusion Centre of Slovenia</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>University Medical Centre Ljubljana</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>University of Ljubljana</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Institute of Oncology Ljubljana</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>
        The goal of this clinical trial is to learn about toxicity of allogeneic mesenchymal stromal&#xD;
        stem cells (MSC, derived from umbilical cord tissue) treatment in head and neck cancer&#xD;
        patients with for post-radiation xerostomia. The main question it aims to answer is the&#xD;
        toxicity of intervention and the secondary objective is to assess preliminary efficacy.&#xD;
        Participants will receive MSC in both parotid and submandibular glands: the toxicity of the&#xD;
        intervention will be assessed using CTCAE v5.0 and its effect will be evaluated through&#xD;
        measuring salivary flow and composition, radiologically (ultrasonography, magnetic resonance&#xD;
        imaging), with scintigraphy and questionnaires. In the control group, salivary gland function&#xD;
        (salivary flow and saliva composition) will be assessed for comparison with the intervention&#xD;
        group.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The aim of the study is to assess the safety and preliminary efficacy of treating xerostomia&#xD;
        with allogeneic mesenchymal stromal stem cells (MSC) derived from umbilical cord tissue. This&#xD;
        is a non-randomized, single-center, non-blinded Phase I study. There will be 10 patients in&#xD;
        the intervention group and 10 healthy volunteers in the control group. In the intervention&#xD;
        group, patients who were successfully treated with (chemo)radiotherapy for oropharyngeal&#xD;
        squamous cell carcinoma two or more years ago and have xerostomia of grade 2 or 3 according&#xD;
        to CTCAE v.5.0 will receive MSC injections under ultrasound guidance into both parotid and&#xD;
        submandibular glands (1 ml syringe with 50×106 MSC and 0.5 ml syringe with 25×106 MSC).&#xD;
        Before the application, measurements of unstimulated and stimulated saliva flow, saliva&#xD;
        composition, and blood parameters (complete blood count, biochemical tests, prothrombin time,&#xD;
        international normalized ratio) will be performed. Magnetic resonance imaging of the glands&#xD;
        (to assess changes in volume, signal, and diffusivity), ultrasound elastography (to assess&#xD;
        gland consistency), salivary gland scintigraphy with pertechnetate ([99mTc]TcO4-, to evaluate&#xD;
        radioisotope uptake in functioning parenchyma and excretory fraction of each gland) and&#xD;
        scintigraphy with hexamethylpropyleneamine oxime ([99mTc]Tc-HMPAO)-labeled MSC (to assess&#xD;
        distribution, retention, and migration of MSC from the site of application) will also be&#xD;
        conducted, along with a biopsy from one of the four glands (to evaluate morphological changes&#xD;
        in glandular tissue). Patients will complete two xerostomia questionnaires and a quality of&#xD;
        life questionnaire European Organization for Research and Treatment of Cancer Quality of Life&#xD;
        H&amp;N35. On the 1st and 5th day after the intervention (day 0), patients will be examined, and&#xD;
        toxicity will be assessed according to CTCAE v5.0. The effect of the intervention will be&#xD;
        evaluated at 4 weeks and 4 months, repeating the tests performed before the intervention,&#xD;
        with the exception of the biopsy and scintigraphy, which will be repeated only 4 months after&#xD;
        the intervention (from the same gland as the first time). In the control group, healthy&#xD;
        individuals will submit saliva samples to determine unstimulated and stimulated saliva flow&#xD;
        and saliva composition (for comparison with the intervention group).&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">August 2025</completion_date>
    <primary_completion_date type="Anticipated">August 2025</primary_completion_date>
    <phase>Phase 1</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>
      <intervention_model_description>intervention group control group</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Safety: Number of patients with serious adverse events</measure>
      <time_frame>4 months</time_frame>
      <description>Registration of number of patients with serious adverse events in a 4 months follow-up period</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Efficacy: Change in unstimulated and stimulated whole salivary flow rate</measure>
      <time_frame>4 months</time_frame>
      <description>Flow rates assessed by sialometry</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Efficacy: Change in saliva composition</measure>
      <time_frame>4 months</time_frame>
      <description>Change in saliva composition</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Efficacy: Change in subjective assessment of xerostomia</measure>
      <time_frame>4 months</time_frame>
      <description>Change in subjective assessment of xerostomia evaluated by Visual Analog Scale (VAS) questionnaire</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Efficacy: Change in quality of life</measure>
      <time_frame>at baseline and 4 weeks and 4 months after intervention</time_frame>
      <description>Change in quality of life evaluated by QLQ-H&amp;N-35 questionnaire</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Efficacy: performance of MSCs application</measure>
      <time_frame>4 months</time_frame>
      <description>Assessed by salivary gland scintigraphy with [99mTc]Tc-HMPAO labeled MSCs</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Efficacy: Salivary gland function</measure>
      <time_frame>4 months</time_frame>
      <description>Assessed by salivary gland scintigraphy with pertechnetate ([99mTc]TcO4-)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Efficacy: salivary gland appearance</measure>
      <time_frame>4 months</time_frame>
      <description>Assessed by magnetic resonance imaging and ultrasonography</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Efficacy: salivary gland structure</measure>
      <time_frame>4 months</time_frame>
      <description>Assessed by histopathological examination of salivary gland tissue sample</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">20</enrollment>
    <condition>Xerostomia Following Radiotherapy</condition>
    <arm_group>
      <arm_group_label>allogeneic mesenchymal stromal stem cells</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Application of allogeneic mesenchymal stromal stem cells (MSC, derived from umbilical cord tissue) under ultrasound guidance into both parotid and submandibular glands.</description>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>allogeneic mesenchymal stromal stem cells</intervention_name>
      <description>mesenchymal stromal stem cells injection under ultrasound guidance into parotid and submandibular glands</description>
      <arm_group_label>allogeneic mesenchymal stromal stem cells</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  squamous cell carcinoma of the oropharynx, Union for International Cancer Control TNM&#xD;
               Classification of Malignant Tumors )8th ed.) clinical stage T1-2N+ or cT3-4cN0-3 M0,&#xD;
               treated with curative intent radiotherapy (tumor dose 66-70 Gy, bilateral neck&#xD;
               irradiation) with or without concurrent chemotherapy&#xD;
  &#xD;
            -  2 years or more post-treatment without signs of locoregional recurrence or systemic&#xD;
               metastasis&#xD;
  &#xD;
            -  non-smoker or former smoker (quit smoking ≥2 years ago)&#xD;
  &#xD;
            -  mean radiation dose &gt;26 Gy to each of the parotid glands and &gt;35 Gy to each of the&#xD;
               submandibular glands&#xD;
  &#xD;
            -  xerostomia of grade 2 or 3, assessed according to the CTCAE v5.0 scale&#xD;
  &#xD;
            -  Clinically reduced salivary flow and hyposalivation (unstimulated whole saliva flow&#xD;
               rate 0.05-0.20 ml/min)&#xD;
  &#xD;
            -  age between 18-75 years&#xD;
  &#xD;
            -  both sexes&#xD;
  &#xD;
            -  signed &quot;Informed Consent Form&quot; for participation in the study&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  newly diagnosed malignancy anywhere in the body within the past two years&#xD;
  &#xD;
            -  active smoker&#xD;
  &#xD;
            -  use of medications with potential to cause dry mouth (e.g., tricyclic antidepressants,&#xD;
               antipsychotics, decongestants, bronchodilators, antihypertensives like beta-blockers&#xD;
               and diuretics, antihistamines, hypnotic sedatives, opioids, and muscle relaxants)&#xD;
  &#xD;
            -  other salivary gland diseases (e.g., Sjögren's syndrome, scleroderma, sialolithiasis,&#xD;
               etc.)&#xD;
  &#xD;
            -  patients on anticoagulant therapy that cannot be discontinued during the intervention&#xD;
  &#xD;
            -  pregnancy or planned pregnancy within the next two years&#xD;
  &#xD;
            -  breastfeeding&#xD;
  &#xD;
            -  active, uncontrolled infection or other medical (including psychiatric) conditions&#xD;
               that, in the researchers' opinion, do not allow for the safe administration of the&#xD;
               planned therapy and performance of the follow-up procedures&#xD;
  &#xD;
            -  known substance abuse or alcoholism&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>75 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Primož Strojan, Prof.</last_name>
      <phone>+38615879290</phone>
      <email>pstrojan@onko-i.si</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Violeta Kaluža</last_name>
      <phone>+38615879122</phone>
      <email>vkaluza@onko-i.si</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Blood Transfusion Center of Slovenia</name>
        <address>
          <city>Ljubljana</city>
          <zip>SI-1000</zip>
          <country>Slovenia</country>
        </address>
      </facility>
      <contact>
        <last_name>Urban Švajger, Prof.</last_name>
        <phone>+386 1 5438 391</phone>
        <email>urban.svajger@ztm.si</email>
      </contact>
      <investigator>
        <last_name>Urban Švajger, Prof.</last_name>
        <role>Principal Investigator</role>
      </investigator>
      <investigator>
        <last_name>Nataša Tešić, Dr.</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Katarina Hartman, Dr.</last_name>
        <role>Sub-Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Institute of Oncology Ljubljana</name>
        <address>
          <city>Ljubljana</city>
          <zip>SI-1000</zip>
          <country>Slovenia</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>University Clinical Center Ljubljana</name>
        <address>
          <city>Ljubljana</city>
          <zip>SI-1000</zip>
          <country>Slovenia</country>
        </address>
      </facility>
      <contact>
        <last_name>Luka Ležaić, MD</last_name>
        <phone>+386 1 522 34 49</phone>
        <email>luka.lezaic@kclj.si</email>
      </contact>
      <investigator>
        <last_name>Luka Ležaić, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Alkaž Sočan, PhD.</last_name>
        <role>Sub-Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>University of Ljubljana</name>
        <address>
          <city>Ljubljana</city>
          <zip>SI-1000</zip>
          <country>Slovenia</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>Slovenia</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 5, 2023</study_first_submitted>
    <study_first_submitted_qc>August 22, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 25, 2023</study_first_posted>
    <last_update_submitted>August 22, 2023</last_update_submitted>
    <last_update_submitted_qc>August 22, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 25, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>post-radiation xerostomia</keyword>
    <keyword>allogenic mesenchyma stromal stem cells</keyword>
    <keyword>toxicity</keyword>
    <keyword>effectiveness</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Xerostomia</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</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/NCT06012604
  org study id: ERIDNPVO-0038/2023
  nct id: NCT06012604
  lead sponsor: 
  collaborator: 
  collaborator: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The goal of this clinical trial is to learn about toxicity of allogeneic mesenchymal stromal
        stem cells (MSC, derived from umbilical cord tissue) treatment in head and neck cancer
        patients with for post-radiation xerostomia. The main question it aims to answer is the
        toxicity of intervention and the secondary objective is to assess preliminary efficacy.
        Participants will receive MSC in both parotid and submandibular glands: the toxicity of the
        intervention will be assessed using CTCAE v5.0 and its effect will be evaluated through
        measuring salivary flow and composition, radiologically (ultrasonography, magnetic resonance
        imaging), with scintigraphy and questionnaires. In the control group, salivary gland function
        (salivary flow and saliva composition) will be assessed for comparison with the intervention
        group.
  The aim of the study is to assess the safety and preliminary efficacy of treating xerostomia
        with allogeneic mesenchymal stromal stem cells (MSC) derived from umbilical cord tissue. This
        is a non-randomized, single-center, non-blinded Phase I study. There will be 10 patients in
        the intervention group and 10 healthy volunteers in the control group. In the intervention
        group, patients who were successfully treated with (chemo)radiotherapy for oropharyngeal
        squamous cell carcinoma two or more years ago and have xerostomia of grade 2 or 3 according
        to CTCAE v.5.0 will receive MSC injections under ultrasound guidance into both parotid and
        submandibular glands (1 ml syringe with 50×106 MSC and 0.5 ml syringe with 25×106 MSC).
        Before the application, measurements of unstimulated and stimulated saliva flow, saliva
        composition, and blood parameters (complete blood count, biochemical tests, prothrombin time,
        international normalized ratio) will be performed. Magnetic resonance imaging of the glands
        (to assess changes in volume, signal, and diffusivity), ultrasound elastography (to assess
        gland consistency), salivary gland scintigraphy with pertechnetate ([99mTc]TcO4-, to evaluate
        radioisotope uptake in functioning parenchyma and excretory fraction of each gland) and
        scintigraphy with hexamethylpropyleneamine oxime ([99mTc]Tc-HMPAO)-labeled MSC (to assess
        distribution, retention, and migration of MSC from the site of application) will also be
        conducted, along with a biopsy from one of the four glands (to evaluate morphological changes
        in glandular tissue). Patients will complete two xerostomia questionnaires and a quality of
        life questionnaire European Organization for Research and Treatment of Cancer Quality of Life
        H&N35. On the 1st and 5th day after the intervention (day 0), patients will be examined, and
        toxicity will be assessed according to CTCAE v5.0. The effect of the intervention will be
        evaluated at 4 weeks and 4 months, repeating the tests performed before the intervention,
        with the exception of the biopsy and scintigraphy, which will be repeated only 4 months after
        the intervention (from the same gland as the first time). In the control group, healthy
        individuals will submit saliva samples to determine unstimulated and stimulated saliva flow
        and saliva composition (for comparison with the intervention group).
  allocation: N/A
  intervention model: Single Group Assignment
  intervention model description: intervention group control group
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Safety: Number of patients with serious adverse events
  time frame: 4 months
  description: Registration of number of patients with serious adverse events in a 4 months follow-up period
  measure: Efficacy: Change in unstimulated and stimulated whole salivary flow rate
  time frame: 4 months
  description: Flow rates assessed by sialometry
  measure: Efficacy: Change in saliva composition
  time frame: 4 months
  description: Change in saliva composition
  measure: Efficacy: Change in subjective assessment of xerostomia
  time frame: 4 months
  description: Change in subjective assessment of xerostomia evaluated by Visual Analog Scale (VAS) questionnaire
  measure: Efficacy: Change in quality of life
  time frame: at baseline and 4 weeks and 4 months after intervention
  description: Change in quality of life evaluated by QLQ-H&N-35 questionnaire
  measure: Efficacy: performance of MSCs application
  time frame: 4 months
  description: Assessed by salivary gland scintigraphy with [99mTc]Tc-HMPAO labeled MSCs
  measure: Efficacy: Salivary gland function
  time frame: 4 months
  description: Assessed by salivary gland scintigraphy with pertechnetate ([99mTc]TcO4-)
  measure: Efficacy: salivary gland appearance
  time frame: 4 months
  description: Assessed by magnetic resonance imaging and ultrasonography
  measure: Efficacy: salivary gland structure
  time frame: 4 months
  description: Assessed by histopathological examination of salivary gland tissue sample
  arm group label: allogeneic mesenchymal stromal stem cells
  arm group type: Experimental
  description: Application of allogeneic mesenchymal stromal stem cells (MSC, derived from umbilical cord tissue) under ultrasound guidance into both parotid and submandibular glands.
  intervention type: Biological
  intervention name: allogeneic mesenchymal stromal stem cells
  description: mesenchymal stromal stem cells injection under ultrasound guidance into parotid and submandibular glands
  arm group label: allogeneic mesenchymal stromal stem cells
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Primož Strojan, Prof.
  phone: +38615879290
  email: pstrojan@onko-i.si
  last name: Violeta Kaluža
  phone: +38615879122
  email: vkaluza@onko-i.si
  facility: 
  contact: 
  investigator: 
  investigator: 
  investigator: 
  facility: 
  facility: 
  contact: 
  investigator: 
  investigator: 
  facility: 
  country: Slovenia
  responsible party type: Sponsor
  mesh term: Xerostomia
  sharing ipd: No