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/NCT05970757</url>
    </required_header>
    <id_info>
      <org_study_id>NL80747.078.22</org_study_id>
      <nct_id>NCT05970757</nct_id>
    </id_info>
    <brief_title>Physiological MRI for Precision Radiotherapy IDH-wildtype Glioblastoma</brief_title>
    <acronym>PhysMRRT</acronym>
    <official_title>Physiological MRI for Precision Radiotherapy IDH-wildtype Glioblastoma</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Erasmus Medical Center</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Erasmus Medical Center</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>
        After surgery, a key step in treatment of patients diagnosed with glioblastoma (high grade&#xD;
        brain tumour) is radiotherapy. The ideal clinical target volume (CTV) for radiotherapy&#xD;
        treatment planning includes all tumour cells remaining after surgery. Currently, the GTV is&#xD;
        delineated on conventional imaging techniques that are only visualizing macroscale structural&#xD;
        changes due to the presence of a large number of tumour cells. After delineating these&#xD;
        visible macroscale changes, the GTV is expanded in all directions with 1.5cm into visibly&#xD;
        healthy tissue to account for microscale tumour invasion. This standard CTV therefore also&#xD;
        contains healthy tissue that should not be receiving radiation, causing side effects of&#xD;
        treatment, hereby reducing quality of life for patients.&#xD;
  &#xD;
        Generating a physiological CTV, in which microscale invasion of tumour cells is taken into&#xD;
        account specifically whilst sparing healthy tissue that is not in need of radiation, is&#xD;
        essential for reducing side effects of radiotherapy. To do so, visualisation is necessary of&#xD;
        physiological processes of tumour cells, which are present before macroscale structural&#xD;
        changes occur. State-of-the-art MRI techniques are now in use at the Erasmus MC that can&#xD;
        assess these physiological processes, including oxygenation status and cell proliferation.&#xD;
  &#xD;
        We aim to generate proof-of-concept of using a physiological CTV for radiotherapy treatment&#xD;
        planning for patients with brain tumours. By extending the clinical standard MRI session used&#xD;
        for radiotherapy planning in 10 patients diagnosed with glioblastoma with advanced MRI&#xD;
        techniques that assess oxygenation status and cell proliferation, we will generate the&#xD;
        physiological CTV including this information and illustrate that it is more precise in&#xD;
        capturing microscale tumour invasion. This proof-of-principle work will be used to obtain&#xD;
        external funding to perform the much needed, and the first of its kind globally, clinical&#xD;
        trial to show the benefit of a physiological CTV for radiotherapy treatment planning in&#xD;
        glioblastoma.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Introduction: After surgery, a key step in treatment of patients diagnosed with glioblastoma&#xD;
        (high grade brain tumour) is radiotherapy. The ideal clinical target volume (CTV) for&#xD;
        radiotherapy treatment planning includes all tumour cells remaining after surgery. Currently,&#xD;
        the GTV is delineated on conventional imaging techniques that are only visualizing macroscale&#xD;
        structural changes due to the presence of a large number of tumour cells. After delineating&#xD;
        these visible macroscale changes, the GTV is expanded in all directions with 1.5cm into&#xD;
        visibly healthy tissue to account for microscale tumour invasion. This standard CTV therefore&#xD;
        also contains healthy tissue that should not be receiving radiation, causing side effects of&#xD;
        treatment, hereby reducing quality of life for patients.&#xD;
  &#xD;
        Generating a physiological CTV, in which microscale invasion of tumour cells is taken into&#xD;
        account specifically whilst sparing healthy tissue that is not in need of radiation, is&#xD;
        essential for reducing side effects of radiotherapy. To do so, visualisation is necessary of&#xD;
        physiological processes of tumour cells, which are present before macroscale structural&#xD;
        changes occur. State-of-the-art MRI techniques are now in use at the Erasmus MC that can&#xD;
        assess these physiological processes, including oxygenation status and cell proliferation.&#xD;
  &#xD;
        We aim to generate proof-of-concept of using a physiological CTV for radiotherapy treatment&#xD;
        planning for patients with brain tumours. By extending the clinical standard MRI session used&#xD;
        for radiotherapy planning in 10 patients diagnosed with glioblastoma with advanced MRI&#xD;
        techniques that assess oxygenation status and cell proliferation, we will generate the&#xD;
        physiological CTV including this information and illustrate that it is more precise in&#xD;
        capturing microscale tumour invasion. This proof-of-principle work will be used to obtain&#xD;
        external funding to perform the much needed, and the first of its kind globally, clinical&#xD;
        trial to show the benefit of a physiological CTV for radiotherapy treatment planning in&#xD;
        glioblastoma.&#xD;
  &#xD;
        Rationale: Current treatment management of patients with IDH-wildtype glioblastoma is&#xD;
        sub-optimal because of two main issues: (1) Creating an accurate target volume for&#xD;
        radiotherapy, a key aspect of glioblastoma treatment, containing all remaining tumour cells&#xD;
        after surgery that is impossible with the conventional CT and MRI imaging techniques&#xD;
        currently used and (2) in the follow-up of patients after radiotherapy, conventional MRI is&#xD;
        incapable of distinguishing tumour progression from treatment effects. The solution to these&#xD;
        issues lies in accurate and non-invasive assessment of physiological processes of tumour&#xD;
        cells to enable delineation of the true physiological clinical target volume (CTV) for&#xD;
        radiotherapy planning and to allow for early detection of true tumour progression during&#xD;
        treatment follow-up.&#xD;
  &#xD;
        Objective: Generate proof-of-concept of using a physiological CTV for radiotherapy treatment&#xD;
        planning for patients with brain tumours.&#xD;
  &#xD;
        Study design: By extending the clinical standard MRI session used for radiotherapy planning&#xD;
        in patients diagnosed with glioblastoma with advanced MRI techniques that assess oxygenation&#xD;
        status and cell proliferation, a physiological CTV will be generated for each patient in&#xD;
        addition to the standard CTV. Treatment for each patient will be according to the current&#xD;
        standard in which the standard CTV is used. Initial analysis will include comparing both CTVs&#xD;
        in terms of volume and location. Patient follow-up will occur according to the clinical&#xD;
        standard, including the standard MRI scan protocols, for a maximum of 2 years.&#xD;
        Pattern-of-failure analysis will be done to compare the standard CTV and physiological CTV.&#xD;
        It is hypothesized that the physiological CTV will be smaller than the standard CTV, whilst&#xD;
        having the same pattern-of-failure.&#xD;
  &#xD;
        Study population: 10 patients (&gt; 18 years), diagnosed with IDH-wildtype glioblastoma, as&#xD;
        confirmed by molecular or immunohistochemistry analysis post resection/biopsy and referred to&#xD;
        outpatient clinic of the department of Radiotherapy to undergo standard treatment with&#xD;
        radiotherapy.&#xD;
  &#xD;
        Intervention (if applicable): Each patient will have an extension to their standard,&#xD;
        radiotherapy planning MRI scan taken for regular clinical care. This scan will last at&#xD;
        maximum 60 minutes.&#xD;
  &#xD;
        Main study parameters/endpoints: Equal prediction of pattern of failure (locations of tumour&#xD;
        recurrence) based on the physiological CTV compared to the standard CTV used for radiotherapy&#xD;
        planning, with the physiological CTV being smaller in volume.&#xD;
  &#xD;
        Nature and extent of the burden and risks associated with participation, benefit and group&#xD;
        relatedness: The patients the burden of prolonged scan time (+ 30 minutes, scan will last 60&#xD;
        mins in total) during their standard RT planning scan. The remainder of their clinical care&#xD;
        will not be altered: RT will be given to these patients based on standard CTVs. Follow-up&#xD;
        will follow the clinical protocol . There will be no personal benefit for the patients in&#xD;
        this research project.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">July 14, 2022</start_date>
    <completion_date type="Anticipated">July 14, 2026</completion_date>
    <primary_completion_date type="Anticipated">July 14, 2026</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>Diagnostic</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Volume and location analysis of physiological and standard CTV</measure>
      <time_frame>Time frame is directly after the extended MRI-acquisition</time_frame>
      <description>Volume and location analysis (Dice correlation coeffcient) will be done to compare the physiological CTVs to standard CTVs generated pre-radiotherapy, where it is hypothesized that the physiological CTVs will be overall smaller in volume and better match microinvasion of the tumour than the standard CTV.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Pattern-of-failure analysis of the physiological and standard CTV</measure>
      <time_frame>1 year</time_frame>
      <description>In the standard follow-up of patients, repeat MRI scans are made every 3 to 4 months. RANO criteria will be used to do response assessment and to determine if and when tumour recurrence is occurring. Pattern-of-failure analysis will then be done with the physiological CTV and the standard CTV, where the percentage of overlap of the recurrence volume with the physiological and standard CTV will be assessed. The hypothesis is that the percentage overlap will not be worse for the physiological CTV compared to the standard CTV, whilst the physiological CTV will be smaller in volume than the standard CTV.</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">10</enrollment>
    <condition>Glioblastoma</condition>
    <arm_group>
      <arm_group_label>Extended MRI group</arm_group_label>
      <arm_group_type>Other</arm_group_type>
      <description>The MRI-scan time is extended with 15-20 minutes.</description>
    </arm_group>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>Extended MRI</intervention_name>
      <description>Extension of the brain tumor MRI-protocol</description>
      <arm_group_label>Extended MRI group</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Informed consent;&#xD;
  &#xD;
            -  Adults (18 years or older);&#xD;
  &#xD;
            -  diagnosed with IDH-wildtype glioblastoma, as confirmed by pathology including&#xD;
               molecular analysis post resection/biopsy;&#xD;
  &#xD;
            -  referred to outpatient clinic of the Department of Radiotherapy to undergo standard&#xD;
               treatment with high-dose RT.&#xD;
  &#xD;
            -  Patients eligible for 30x2Gy or 15x2.67Gy&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Contraindication for MRI&#xD;
  &#xD;
            -  Contraindication for use of gadolinium-based contrast agent (i.e. subject having renal&#xD;
               deficiency)&#xD;
  &#xD;
            -  Unable to give informed consent&#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>Patrick Tang, MSc</last_name>
      <role>Study Director</role>
      <affiliation>Erasmus Medical Center</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Patrick Tang, MSc</last_name>
      <phone>+31634271995</phone>
      <email>p.l.y.tang@erasmusmc.nl</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Laurens Groenendijk</last_name>
      <phone>+31107033612</phone>
      <email>imaging.trialbureau@erasmusmc.nl</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Erasmus Medical Center</name>
        <address>
          <city>Rotterdam</city>
          <state>Zuid-Holland</state>
          <zip>3015GD</zip>
          <country>Netherlands</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Patrick Tang, MSc</last_name>
        <phone>+31634271995</phone>
        <email>p.l.y.tang@erasmusmc.nl</email>
      </contact>
      <contact_backup>
        <last_name>Laurens Groenendijk</last_name>
        <phone>+31107033612</phone>
        <email>imaging.trialbureau@erasmusmc.nl</email>
      </contact_backup>
      <investigator>
        <last_name>Esther Warnert, PhD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>Netherlands</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 24, 2023</study_first_submitted>
    <study_first_submitted_qc>July 24, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 1, 2023</study_first_posted>
    <last_update_submitted>July 24, 2023</last_update_submitted>
    <last_update_submitted_qc>July 24, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 1, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Erasmus Medical Center</investigator_affiliation>
      <investigator_full_name>Esther Warnert</investigator_full_name>
      <investigator_title>Assistant professor - Radiology &amp; Nuclear medicine</investigator_title>
    </responsible_party>
    <keyword>Glioblastoma</keyword>
    <keyword>Precision radiotherapy</keyword>
    <keyword>Advanced MRI</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Glioblastoma</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
      <ipd_description>Not available yet</ipd_description>
    </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/NCT05970757
  org study id: NL80747.078.22
  nct id: NCT05970757
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  After surgery, a key step in treatment of patients diagnosed with glioblastoma (high grade
        brain tumour) is radiotherapy. The ideal clinical target volume (CTV) for radiotherapy
        treatment planning includes all tumour cells remaining after surgery. Currently, the GTV is
        delineated on conventional imaging techniques that are only visualizing macroscale structural
        changes due to the presence of a large number of tumour cells. After delineating these
        visible macroscale changes, the GTV is expanded in all directions with 1.5cm into visibly
        healthy tissue to account for microscale tumour invasion. This standard CTV therefore also
        contains healthy tissue that should not be receiving radiation, causing side effects of
        treatment, hereby reducing quality of life for patients.
  
        Generating a physiological CTV, in which microscale invasion of tumour cells is taken into
        account specifically whilst sparing healthy tissue that is not in need of radiation, is
        essential for reducing side effects of radiotherapy. To do so, visualisation is necessary of
        physiological processes of tumour cells, which are present before macroscale structural
        changes occur. State-of-the-art MRI techniques are now in use at the Erasmus MC that can
        assess these physiological processes, including oxygenation status and cell proliferation.
  
        We aim to generate proof-of-concept of using a physiological CTV for radiotherapy treatment
        planning for patients with brain tumours. By extending the clinical standard MRI session used
        for radiotherapy planning in 10 patients diagnosed with glioblastoma with advanced MRI
        techniques that assess oxygenation status and cell proliferation, we will generate the
        physiological CTV including this information and illustrate that it is more precise in
        capturing microscale tumour invasion. This proof-of-principle work will be used to obtain
        external funding to perform the much needed, and the first of its kind globally, clinical
        trial to show the benefit of a physiological CTV for radiotherapy treatment planning in
        glioblastoma.
  Introduction: After surgery, a key step in treatment of patients diagnosed with glioblastoma
        (high grade brain tumour) is radiotherapy. The ideal clinical target volume (CTV) for
        radiotherapy treatment planning includes all tumour cells remaining after surgery. Currently,
        the GTV is delineated on conventional imaging techniques that are only visualizing macroscale
        structural changes due to the presence of a large number of tumour cells. After delineating
        these visible macroscale changes, the GTV is expanded in all directions with 1.5cm into
        visibly healthy tissue to account for microscale tumour invasion. This standard CTV therefore
        also contains healthy tissue that should not be receiving radiation, causing side effects of
        treatment, hereby reducing quality of life for patients.
  
        Generating a physiological CTV, in which microscale invasion of tumour cells is taken into
        account specifically whilst sparing healthy tissue that is not in need of radiation, is
        essential for reducing side effects of radiotherapy. To do so, visualisation is necessary of
        physiological processes of tumour cells, which are present before macroscale structural
        changes occur. State-of-the-art MRI techniques are now in use at the Erasmus MC that can
        assess these physiological processes, including oxygenation status and cell proliferation.
  
        We aim to generate proof-of-concept of using a physiological CTV for radiotherapy treatment
        planning for patients with brain tumours. By extending the clinical standard MRI session used
        for radiotherapy planning in 10 patients diagnosed with glioblastoma with advanced MRI
        techniques that assess oxygenation status and cell proliferation, we will generate the
        physiological CTV including this information and illustrate that it is more precise in
        capturing microscale tumour invasion. This proof-of-principle work will be used to obtain
        external funding to perform the much needed, and the first of its kind globally, clinical
        trial to show the benefit of a physiological CTV for radiotherapy treatment planning in
        glioblastoma.
  
        Rationale: Current treatment management of patients with IDH-wildtype glioblastoma is
        sub-optimal because of two main issues: (1) Creating an accurate target volume for
        radiotherapy, a key aspect of glioblastoma treatment, containing all remaining tumour cells
        after surgery that is impossible with the conventional CT and MRI imaging techniques
        currently used and (2) in the follow-up of patients after radiotherapy, conventional MRI is
        incapable of distinguishing tumour progression from treatment effects. The solution to these
        issues lies in accurate and non-invasive assessment of physiological processes of tumour
        cells to enable delineation of the true physiological clinical target volume (CTV) for
        radiotherapy planning and to allow for early detection of true tumour progression during
        treatment follow-up.
  
        Objective: Generate proof-of-concept of using a physiological CTV for radiotherapy treatment
        planning for patients with brain tumours.
  
        Study design: By extending the clinical standard MRI session used for radiotherapy planning
        in patients diagnosed with glioblastoma with advanced MRI techniques that assess oxygenation
        status and cell proliferation, a physiological CTV will be generated for each patient in
        addition to the standard CTV. Treatment for each patient will be according to the current
        standard in which the standard CTV is used. Initial analysis will include comparing both CTVs
        in terms of volume and location. Patient follow-up will occur according to the clinical
        standard, including the standard MRI scan protocols, for a maximum of 2 years.
        Pattern-of-failure analysis will be done to compare the standard CTV and physiological CTV.
        It is hypothesized that the physiological CTV will be smaller than the standard CTV, whilst
        having the same pattern-of-failure.
  
        Study population: 10 patients (> 18 years), diagnosed with IDH-wildtype glioblastoma, as
        confirmed by molecular or immunohistochemistry analysis post resection/biopsy and referred to
        outpatient clinic of the department of Radiotherapy to undergo standard treatment with
        radiotherapy.
  
        Intervention (if applicable): Each patient will have an extension to their standard,
        radiotherapy planning MRI scan taken for regular clinical care. This scan will last at
        maximum 60 minutes.
  
        Main study parameters/endpoints: Equal prediction of pattern of failure (locations of tumour
        recurrence) based on the physiological CTV compared to the standard CTV used for radiotherapy
        planning, with the physiological CTV being smaller in volume.
  
        Nature and extent of the burden and risks associated with participation, benefit and group
        relatedness: The patients the burden of prolonged scan time (+ 30 minutes, scan will last 60
        mins in total) during their standard RT planning scan. The remainder of their clinical care
        will not be altered: RT will be given to these patients based on standard CTVs. Follow-up
        will follow the clinical protocol . There will be no personal benefit for the patients in
        this research project.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Diagnostic
  masking: None (Open Label)
  measure: Volume and location analysis of physiological and standard CTV
  time frame: Time frame is directly after the extended MRI-acquisition
  description: Volume and location analysis (Dice correlation coeffcient) will be done to compare the physiological CTVs to standard CTVs generated pre-radiotherapy, where it is hypothesized that the physiological CTVs will be overall smaller in volume and better match microinvasion of the tumour than the standard CTV.
  measure: Pattern-of-failure analysis of the physiological and standard CTV
  time frame: 1 year
  description: In the standard follow-up of patients, repeat MRI scans are made every 3 to 4 months. RANO criteria will be used to do response assessment and to determine if and when tumour recurrence is occurring. Pattern-of-failure analysis will then be done with the physiological CTV and the standard CTV, where the percentage of overlap of the recurrence volume with the physiological and standard CTV will be assessed. The hypothesis is that the percentage overlap will not be worse for the physiological CTV compared to the standard CTV, whilst the physiological CTV will be smaller in volume than the standard CTV.
  arm group label: Extended MRI group
  arm group type: Other
  description: The MRI-scan time is extended with 15-20 minutes.
  intervention type: Diagnostic Test
  intervention name: Extended MRI
  description: Extension of the brain tumor MRI-protocol
  arm group label: Extended MRI group
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Patrick Tang, MSc
  role: Study Director
  affiliation: Erasmus Medical Center
  last name: Patrick Tang, MSc
  phone: +31634271995
  email: p.l.y.tang@erasmusmc.nl
  last name: Laurens Groenendijk
  phone: +31107033612
  email: imaging.trialbureau@erasmusmc.nl
  facility: 
  status: Recruiting
  contact: 
  contact backup: 
  investigator: 
  country: Netherlands
  responsible party type: Principal Investigator
  investigator affiliation: Erasmus Medical Center
  investigator full name: Esther Warnert
  investigator title: Assistant professor - Radiology & Nuclear medicine
  mesh term: Glioblastoma
  sharing ipd: Undecided
  ipd description: Not available yet