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/NCT05977803</url>
    </required_header>
    <id_info>
      <org_study_id>APHP230263</org_study_id>
      <nct_id>NCT05977803</nct_id>
    </id_info>
    <brief_title>Contribution of the CEST Sequence in the Characterization of Radionecrosis of Brain Metastases of Pulmonary Origin</brief_title>
    <acronym>ACROP</acronym>
    <official_title>Contribution of the CEST Sequence in the Characterization of Radionecrosis of Brain Metastases of Pulmonary Origin</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Assistance Publique - Hôpitaux de Paris</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Assistance Publique - Hôpitaux de Paris</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>
        The aim of the study is to determine whether the use of the CEST sequence would have&#xD;
        diagnostic performance equivalent to the reference method of T2* infusion with contrast&#xD;
        injection in the diagnosis of radionecrosis of lung cancer brain metastases.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Brain metastases are frequent secondary sites in the evolution of cancers, with an incidence&#xD;
        of all cancers combined of about 20% and up to 40% in the later phases of the disease. Among&#xD;
        these metastases, the lung is the most common primary lesion (responsible for 20-56% of brain&#xD;
        metastases). The overall prognosis for metastatic brain cancers is poor, with treatment-free&#xD;
        survival of 1 to 2 months, and with treatment averaging 7-8 months. Their treatment is based&#xD;
        on systemic medical treatment (chemotherapy, immunotherapy or targeted therapy depending on&#xD;
        the status of the lesion) and on the other hand on the response to local treatment (surgery&#xD;
        or radiotherapy). Radiotherapy is performed either as a first-line or post-operative&#xD;
        depending on the resectability of the lesions and the operability of the patient.&#xD;
  &#xD;
        Radionecrosis is a late complication (6 months to 2 years on average) and frequent (5-25%) of&#xD;
        stereotactic radiotherapy. It may be promoted by the concomitant use of immunotherapy such as&#xD;
        checkpoint inhibitors, which implies a probable increase in its incidence. Treatment of&#xD;
        radionecrosis is based on corticosteroids; recent studies also propose Bevacizumab.&#xD;
  &#xD;
        The distinction in MRI between tumor progression and radionecrosis is based on a multimodal&#xD;
        approach. Indeed, conventional sequences alone have average performance (sensitivity 76% and&#xD;
        specificity 59%). Several MRI methods have been evaluated, but their performance varies&#xD;
        according to the studies. Cerebral perfusion is the most widely used method, requiring&#xD;
        contrast injection with correct performance. However, there is no standardized perfusion&#xD;
        value to directly extrapolate these results. MRI spectroscopy has also been studied, with&#xD;
        correct performance but only evaluated on weak samples and retrospectively.&#xD;
  &#xD;
        CEST is an MRI technique that uses endogenous contrast, i.e. does not require injection of&#xD;
        contrast medium. It consists of specifically altering the signal of a molecular compound by&#xD;
        causing saturation (i.e. cancellation of its signal) and studying the saturation of the&#xD;
        solute (i.e. water) on contact. Indeed, due to a process called 'chemical saturation&#xD;
        transfer', the signal from the water in contact with the targeted compound will also become&#xD;
        partially saturated. The subtraction of the MRI signals acquired before and after saturation&#xD;
        makes it possible to obtain a tissue mapping of the molecular compound initially targeted&#xD;
        obtaining an indirect reflection of its concentration. Indeed, the macromolecular composition&#xD;
        of tissues (inaccessible for physical reasons in spectroscopy) differs according to&#xD;
        radionecrosis status or tumor progression, with more &quot;&quot;amide&quot;&quot; compounds in the second case.&#xD;
  &#xD;
        This relatively recent development technique has been studied in primary and secondary brain&#xD;
        tumors, especially in the context of radionecrosis, but mainly in primary brain tumors. It&#xD;
        seems to allow a more precise and earlier detection of possible tumor progressions.&#xD;
  &#xD;
        The diagnosis of radionecrosis is therefore a major step forward for the management of&#xD;
        patients with irradiated brain metastases.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">September 2026</completion_date>
    <primary_completion_date type="Anticipated">September 2025</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>Visually significant hyperperfusion on normalized cerebral blood flow mapping generated from T2* infusion data with injection, confirmed by quantitative measurement of a ratio &gt; 2.5 between tumor DSC and contralateral white matter.</measure>
      <time_frame>24 months</time_frame>
      <description>Diagnostic performance of the CEST sequence in the diagnosis of radionecrosis on irradiated metastases of primary lung cancer compared to injected T2* infusion sequence</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Diagnostic performances for the IVIM sequence using IVIM scattering derivatives: f', ADC</measure>
      <time_frame>24 months</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Diagnostic performances for the ASL (arterial spin labeling) sequence using ASL infusion derivatives: intralesional CBF (cerebral blood flow) relative to contralateral white matter CBF</measure>
      <time_frame>24 months</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Diagnostic performances of coupled CEST, IVIM and ASL sequences, evaluated by the derivates of the CEST sequence : APT-AUC (Area Under Curve), NOE-MTR (Magnetization Transfer Ratio) and NOE-AUC.</measure>
      <time_frame>24 months</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Diagnostic performances of coupled CEST, IVIM and ASL sequences, evaluated by the derivates of the IVIM scattering : f', ADC</measure>
      <time_frame>24 months</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Diagnostic performance of coupled CEST, IVIM and ASL sequences, evaluated by the derivates of the ASL infusion : intralesional CBF (cerebral blood flow) relative to contralateral white matter CBF</measure>
      <time_frame>24 months</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Tolerance of acquisition of all CEST, IVIM and ASL sequences evaluated by the percentage of exams interrupted.</measure>
      <time_frame>24 months</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Describtion of non-tumor white matter changes in the irradiation field and outside the CEST sequence irradiation field during follow-up</measure>
      <time_frame>24 months</time_frame>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">60</enrollment>
    <condition>Brain Metastases</condition>
    <condition>Radionecrosis</condition>
    <condition>Pulmonary Cancer</condition>
    <arm_group>
      <arm_group_label>Radiation therapy</arm_group_label>
      <arm_group_type>Other</arm_group_type>
      <description>Patient treated for metastatic cerebral lung cancer who has been treated with external beam radiotherapy such as in toto brain irradiation or stereotactic radiosurgery followed in the thoracic oncology department of Bichat Hospital.</description>
    </arm_group>
    <intervention>
      <intervention_type>Radiation</intervention_type>
      <intervention_name>MRI with CEST sequence, IVIM and ASL sequence</intervention_name>
      <description>Three sequences will be added as part of the protocol (for an additional duration of about 10 minutes) :&#xD;
  The CEST sequence&#xD;
  The ASL infusion sequence&#xD;
  The IVIM sequence</description>
      <arm_group_label>Radiation therapy</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Patients &gt; 18 years of age&#xD;
  &#xD;
            -  Histologically proven primary lung cancer&#xD;
  &#xD;
            -  Histologically proven or not brain metastases&#xD;
  &#xD;
            -  Irradiated metastases&#xD;
  &#xD;
            -  Inclusion in a treatment protocol for brain metastases by brain metastasis in toto or&#xD;
               stereotactic or gamma-knife radiotherapy&#xD;
  &#xD;
            -  Morphological increase of one or more lesions of secondary brain metastases on a&#xD;
               follow-up MRI&#xD;
  &#xD;
            -  Patients affiliated to a social security scheme&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Opposition to the study&#xD;
  &#xD;
            -  Contraindication to MRI&#xD;
  &#xD;
            -  Refusal of imaging by the patient&#xD;
  &#xD;
            -  Patient with state medical aid (unless exemption from affiliation)&#xD;
  &#xD;
            -  Severe cognitive impairment making informed consent impossible&#xD;
  &#xD;
            -  Patients under guardianship or deprived of liberty&#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>Augustin Gaudemer, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Assistance Publique - Hôpitaux de Paris</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Augustin Gaudemer, MD</last_name>
      <phone>01 40 25 76 13</phone>
      <email>augustin.gaudemer@aphp.fr</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Marie-Cécile Henry-Feugeas, MD</last_name>
      <phone>01 40 25 81 52</phone>
      <email>marie-cecile.henry-feugeas@aphp.fr</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Hôpital Bichat-Claude Bernard</name>
        <address>
          <city>Paris</city>
          <zip>75018</zip>
          <country>France</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>France</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>June 21, 2023</study_first_submitted>
    <study_first_submitted_qc>August 3, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 4, 2023</study_first_posted>
    <last_update_submitted>August 3, 2023</last_update_submitted>
    <last_update_submitted_qc>August 3, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 4, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>radionecrosis, metastases,</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Neoplasm Metastasis</mesh_term>
      <mesh_term>Brain Neoplasms</mesh_term>
      <mesh_term>Lung Neoplasms</mesh_term>
    </condition_browse>
    <!-- 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/NCT05977803
  org study id: APHP230263
  nct id: NCT05977803
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  The aim of the study is to determine whether the use of the CEST sequence would have
        diagnostic performance equivalent to the reference method of T2* infusion with contrast
        injection in the diagnosis of radionecrosis of lung cancer brain metastases.
  Brain metastases are frequent secondary sites in the evolution of cancers, with an incidence
        of all cancers combined of about 20% and up to 40% in the later phases of the disease. Among
        these metastases, the lung is the most common primary lesion (responsible for 20-56% of brain
        metastases). The overall prognosis for metastatic brain cancers is poor, with treatment-free
        survival of 1 to 2 months, and with treatment averaging 7-8 months. Their treatment is based
        on systemic medical treatment (chemotherapy, immunotherapy or targeted therapy depending on
        the status of the lesion) and on the other hand on the response to local treatment (surgery
        or radiotherapy). Radiotherapy is performed either as a first-line or post-operative
        depending on the resectability of the lesions and the operability of the patient.
  
        Radionecrosis is a late complication (6 months to 2 years on average) and frequent (5-25%) of
        stereotactic radiotherapy. It may be promoted by the concomitant use of immunotherapy such as
        checkpoint inhibitors, which implies a probable increase in its incidence. Treatment of
        radionecrosis is based on corticosteroids; recent studies also propose Bevacizumab.
  
        The distinction in MRI between tumor progression and radionecrosis is based on a multimodal
        approach. Indeed, conventional sequences alone have average performance (sensitivity 76% and
        specificity 59%). Several MRI methods have been evaluated, but their performance varies
        according to the studies. Cerebral perfusion is the most widely used method, requiring
        contrast injection with correct performance. However, there is no standardized perfusion
        value to directly extrapolate these results. MRI spectroscopy has also been studied, with
        correct performance but only evaluated on weak samples and retrospectively.
  
        CEST is an MRI technique that uses endogenous contrast, i.e. does not require injection of
        contrast medium. It consists of specifically altering the signal of a molecular compound by
        causing saturation (i.e. cancellation of its signal) and studying the saturation of the
        solute (i.e. water) on contact. Indeed, due to a process called 'chemical saturation
        transfer', the signal from the water in contact with the targeted compound will also become
        partially saturated. The subtraction of the MRI signals acquired before and after saturation
        makes it possible to obtain a tissue mapping of the molecular compound initially targeted
        obtaining an indirect reflection of its concentration. Indeed, the macromolecular composition
        of tissues (inaccessible for physical reasons in spectroscopy) differs according to
        radionecrosis status or tumor progression, with more ""amide"" compounds in the second case.
  
        This relatively recent development technique has been studied in primary and secondary brain
        tumors, especially in the context of radionecrosis, but mainly in primary brain tumors. It
        seems to allow a more precise and earlier detection of possible tumor progressions.
  
        The diagnosis of radionecrosis is therefore a major step forward for the management of
        patients with irradiated brain metastases.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Diagnostic
  masking: None (Open Label)
  measure: Visually significant hyperperfusion on normalized cerebral blood flow mapping generated from T2* infusion data with injection, confirmed by quantitative measurement of a ratio > 2.5 between tumor DSC and contralateral white matter.
  time frame: 24 months
  description: Diagnostic performance of the CEST sequence in the diagnosis of radionecrosis on irradiated metastases of primary lung cancer compared to injected T2* infusion sequence
  measure: Diagnostic performances for the IVIM sequence using IVIM scattering derivatives: f', ADC
  time frame: 24 months
  measure: Diagnostic performances for the ASL (arterial spin labeling) sequence using ASL infusion derivatives: intralesional CBF (cerebral blood flow) relative to contralateral white matter CBF
  time frame: 24 months
  measure: Diagnostic performances of coupled CEST, IVIM and ASL sequences, evaluated by the derivates of the CEST sequence : APT-AUC (Area Under Curve), NOE-MTR (Magnetization Transfer Ratio) and NOE-AUC.
  time frame: 24 months
  measure: Diagnostic performances of coupled CEST, IVIM and ASL sequences, evaluated by the derivates of the IVIM scattering : f', ADC
  time frame: 24 months
  measure: Diagnostic performance of coupled CEST, IVIM and ASL sequences, evaluated by the derivates of the ASL infusion : intralesional CBF (cerebral blood flow) relative to contralateral white matter CBF
  time frame: 24 months
  measure: Tolerance of acquisition of all CEST, IVIM and ASL sequences evaluated by the percentage of exams interrupted.
  time frame: 24 months
  measure: Describtion of non-tumor white matter changes in the irradiation field and outside the CEST sequence irradiation field during follow-up
  time frame: 24 months
  arm group label: Radiation therapy
  arm group type: Other
  description: Patient treated for metastatic cerebral lung cancer who has been treated with external beam radiotherapy such as in toto brain irradiation or stereotactic radiosurgery followed in the thoracic oncology department of Bichat Hospital.
  intervention type: Radiation
  intervention name: MRI with CEST sequence, IVIM and ASL sequence
  description: Three sequences will be added as part of the protocol (for an additional duration of about 10 minutes) :
  The CEST sequence
  The ASL infusion sequence
  The IVIM sequence
  arm group label: Radiation therapy
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Augustin Gaudemer, MD
  role: Principal Investigator
  affiliation: Assistance Publique - Hôpitaux de Paris
  last name: Augustin Gaudemer, MD
  phone: 01 40 25 76 13
  email: augustin.gaudemer@aphp.fr
  last name: Marie-Cécile Henry-Feugeas, MD
  phone: 01 40 25 81 52
  email: marie-cecile.henry-feugeas@aphp.fr
  facility: 
  country: France
  responsible party type: Sponsor
  mesh term: Neoplasm Metastasis
  mesh term: Brain Neoplasms
  mesh term: Lung Neoplasms