<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/NCT01703962</url>
  </required_header>
  <id_info>
    <org_study_id>C11-28</org_study_id>
    <secondary_id>2011-A01356-35</secondary_id>
    <nct_id>NCT01703962</nct_id>
  </id_info>
  <brief_title>Non Invasive IDentification of Gliomas With IDH1 Mutation</brief_title>
  <acronym>IDASPE</acronym>
  <official_title>Non Invasive IDentification of Gliomas With IDH1 Mutation by Free Plasmatic DNA Analysis, 2-hydroxyglutarate Dosage in the Urines and 2-hydroxyglutarate Detection by Brain SPEctro-MRI: Diagnostic and Follow-up Application (IDASPE)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institut National de la Santé Et de la Recherche Médicale, France</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Institut National de la Santé Et de la Recherche Médicale, France</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The recurrent mutation IDH1Arg132His leads to the cellular accumulation of&#xD;
      D-2-hydroxyglutarate (2-HG), thus representing a diagnostic marker (this change is almost&#xD;
      specific for gliomas) and prognostic (mutated gliomas have longer survival) of interest.&#xD;
&#xD;
      The main objective is to identify the patients with IDH1 mutated glioma by three&#xD;
      complementary approaches -genetic (identification of IDH1 mutation in plasmatic DNA),&#xD;
      biochemical (2-HG dosage in the urine of patients) and radiological (2-HG&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Our preliminary results indicate an extremely high amount of D-2HG in gliomas and CSF of the&#xD;
      patients, and therefore the possibility to detect its presence by spectro-MRI, and to&#xD;
      establish a non-invasive diagnosis of glioma with IDH1 mutation. Our goal is to identify and&#xD;
      quantify by high-field MRI spectroscopy the presence of D-2HG to identify gliomas with IDH1&#xD;
      mutation. In parallel, we developed a technique for selective amplification of the mutated&#xD;
      form of IDH1 (COLD PCR): by combining this technique with digital PCR, we already are able to&#xD;
      detect IDH1 mutation from free plasma DNA with a sensitivity of 58% and a specificity of&#xD;
      100%. At the same time we have shown that D-2HG levels in urine of patients correlate with&#xD;
      the status of the tumor IDH1.&#xD;
&#xD;
      The main objective is to identify using this triple approach (detection of the mutation on&#xD;
      plasma DNA detection, detection of urinary D-2HG, detection of tumor D-2HG by spectro-MRI)&#xD;
      patients with IDH1arg132His mutation, the secondary objective is to evaluate the value of&#xD;
      these markers for patients follow-up and for differentiating recurrence from treatment&#xD;
      induced damage. 40 patients with grade II and grade III gliomas (20 mutated, 20 non mutated)&#xD;
      will be included and followed up for one year (five measurements are planned).&#xD;
&#xD;
      The first interest is diagnostic: the presence of the IDH1Arg132His mutation allows the&#xD;
      diagnosis of glioma. This information is particularly valuable in patients not amenable to&#xD;
      biopsy, because of the location of the tumor considered at risk, the general condition of the&#xD;
      patient or the co-morbidities and medications. We hope also with these parameters to better&#xD;
      monitor patient's follow-up, and to have a new method to differentiate tumor recurrence and&#xD;
      radionecrosis or post-radiation leukoencephalopathy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 14, 2012</start_date>
  <completion_date type="Actual">March 20, 2014</completion_date>
  <primary_completion_date type="Actual">March 2014</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">6</enrollment>
  <condition>Non Invasive Diagnosis of Glioma</condition>
  <arm_group>
    <arm_group_label>Patients with IDH1 R132H or wild type IDH1/IDH2 glioma</arm_group_label>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Plasma samples containing free DNA fragments Urine&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients will be recruited from the active file of patients with glioma II or III, followed&#xD;
        at the Pitié-Salpetrière Hospital, and whose status is known for IDH1.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Inclusion Criteria&#xD;
&#xD;
          -  Affiliated to Health Insurance regimen (sécurité sociale)&#xD;
&#xD;
          -  Patient of 18 years or more&#xD;
&#xD;
          -  written informed consent&#xD;
&#xD;
          -  Glioma grade II or III histologically proven&#xD;
&#xD;
          -  Frozen samples available&#xD;
&#xD;
          -  Known status IDH1/IDH2&#xD;
&#xD;
          -  Presence of a measurable residual tumor (&gt; 2 cm in diameter FLAIR)&#xD;
&#xD;
          -  Karnofsky Performance Status (KPS)&gt; 60&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Contraindication to MRI *&#xD;
&#xD;
          -  The rare patients with IDH2 mutation or with non Arg132His IDH1 mutation will be&#xD;
             excluded&#xD;
&#xD;
          -  Inability to provide informed consent&#xD;
&#xD;
          -  Patient under guardianship or deprived of liberty by court&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Marc SANSON, MDPhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pittsburgh</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>GH Pitié-Salpêtrière, 47 Bd de l'Hopital,</name>
      <address>
        <city>Paris</city>
        <state>Sélectionner...</state>
        <zip>75013</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>October 8, 2012</study_first_submitted>
  <study_first_submitted_qc>October 8, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 11, 2012</study_first_posted>
  <last_update_submitted>August 25, 2021</last_update_submitted>
  <last_update_submitted_qc>August 25, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 26, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Glioma</keyword>
  <keyword>IDH1</keyword>
  <keyword>Spectroscopy</keyword>
  <keyword>Plasma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glioma</mesh_term>
  </condition_browse>
  <!-- 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/NCT01703962
org study id: C11-28
secondary id: 2011-A01356-35
nct id: NCT01703962
lead sponsor: 
has dmc: No
The recurrent mutation IDH1Arg132His leads to the cellular accumulation of
      D-2-hydroxyglutarate (2-HG), thus representing a diagnostic marker (this change is almost
      specific for gliomas) and prognostic (mutated gliomas have longer survival) of interest.

      The main objective is to identify the patients with IDH1 mutated glioma by three
      complementary approaches -genetic (identification of IDH1 mutation in plasmatic DNA),
      biochemical (2-HG dosage in the urine of patients) and radiological (2-HG
Our preliminary results indicate an extremely high amount of D-2HG in gliomas and CSF of the
      patients, and therefore the possibility to detect its presence by spectro-MRI, and to
      establish a non-invasive diagnosis of glioma with IDH1 mutation. Our goal is to identify and
      quantify by high-field MRI spectroscopy the presence of D-2HG to identify gliomas with IDH1
      mutation. In parallel, we developed a technique for selective amplification of the mutated
      form of IDH1 (COLD PCR): by combining this technique with digital PCR, we already are able to
      detect IDH1 mutation from free plasma DNA with a sensitivity of 58% and a specificity of
      100%. At the same time we have shown that D-2HG levels in urine of patients correlate with
      the status of the tumor IDH1.

      The main objective is to identify using this triple approach (detection of the mutation on
      plasma DNA detection, detection of urinary D-2HG, detection of tumor D-2HG by spectro-MRI)
      patients with IDH1arg132His mutation, the secondary objective is to evaluate the value of
      these markers for patients follow-up and for differentiating recurrence from treatment
      induced damage. 40 patients with grade II and grade III gliomas (20 mutated, 20 non mutated)
      will be included and followed up for one year (five measurements are planned).

      The first interest is diagnostic: the presence of the IDH1Arg132His mutation allows the
      diagnosis of glioma. This information is particularly valuable in patients not amenable to
      biopsy, because of the location of the tumor considered at risk, the general condition of the
      patient or the co-morbidities and medications. We hope also with these parameters to better
      monitor patient's follow-up, and to have a new method to differentiate tumor recurrence and
      radionecrosis or post-radiation leukoencephalopathy.
observational model: Case-Control
time perspective: Prospective
arm group label: Patients with IDH1 R132H or wild type IDH1/IDH2 glioma
Plasma samples containing free DNA fragments Urine
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Marc SANSON, MDPhD
role: Principal Investigator
affiliation: University of Pittsburgh
facility: 
country: France
responsible party type: Sponsor
mesh term: Glioma