<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/NCT03257618</url>
  </required_header>
  <id_info>
    <org_study_id>ICM-URC2016-32</org_study_id>
    <nct_id>NCT03257618</nct_id>
  </id_info>
  <brief_title>Quality of Life and Neurocognitive Functioning</brief_title>
  <acronym>TEMOIN</acronym>
  <official_title>Quality of Life and Neurocognitive Functioning in Diffuse Low-grade Glioma (TEMOIN)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institut du Cancer de Montpellier - Val d'Aurelle</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Institut du Cancer de Montpellier - Val d'Aurelle</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>
      Studying QoL in patients DLGG receiving TMZ is complex because of the multiples interactions&#xD;
      between tumor characteristics, neurocognitive functioning, treatments, environment and&#xD;
      psychopathological context in which these patients experience symptoms. It is, however,&#xD;
      important to accurately evaluate these aspects in consideration of the young age, generally&#xD;
      preserved QoL at the time of diagnosis, possible implications of the disease on the&#xD;
      professional (DLGG patients are often still active), social and familial domain, and&#xD;
      relatively long survival of these patients. In the absence of a curative treatment for DLGG,&#xD;
      preserving patients' QoL is indeed a major goal.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Diffuse low-grade gliomas (DLGG) (or WHO grade II gliomas, Louis et al., 2007) are rare&#xD;
      tumors, with an incidence estimated at 1/105 person-year (Ostrom et al., 2015). They affect&#xD;
      young people in their thirties or forties (Capelle et al., 2013). DLGG are characterized by a&#xD;
      continuous growth and an unavoidable anaplastic transformation (Mandonnet et al., 2003).&#xD;
      Epilepsy is the main presenting mode while neurological deficits are rare at diagnosis due to&#xD;
      the brain plasticity allowed by the usually slow growth speed of these tumors. However,&#xD;
      frequent alterations in cognitive functions (including mostly memory, executive functioning,&#xD;
      and attention) have been described (Racine et al., 2015). The prognosis of DLGG is variable&#xD;
      (Pignatti et al., 2002) and overall survival (OS) ranges from 5 years to 15 years according&#xD;
      to several factors, including the tumor phenotype, the isocitrate dehydrogenase (IDH)&#xD;
      mutation and the 1p19q codeletion, the tumor volume at diagnosis, and the tumor spontaneous&#xD;
      growth speed (Capelle et al., 2013).&#xD;
&#xD;
      The prognostic impact of the extent of surgery has now been well demonstrated (Jakola et al.,&#xD;
      2012; Duffau 2016) and surgery is now the first treatment option (Soffietti et al., 2010). In&#xD;
      unresectable DLGG or in patients with a progressive disease after surgery (with no&#xD;
      possibility of a second surgery), several treatment options have been investigated, including&#xD;
      radiation therapy (RT) and chemotherapy, but to date the timing and choice of treatment&#xD;
      remains controversial. RT can be efficient in DLGG, however, the EORTC 22845 phase III trial&#xD;
      found that early RT has no impact on OS compared to late RT, despite an increased&#xD;
      progression-free survival (PFS) (van Den Bent et al., 2005). Moreover, some evidence of late&#xD;
      decreased neurocognitive functioning has been consistently reported following RT (Klein et&#xD;
      al., 2002; Douw et al., 2009). Because of this potential neurotoxicity and the absence of a&#xD;
      benefit on OS of early RT, many neuro-oncological teams now only offer RT to patients with a&#xD;
      progressive disease after chemotherapy.&#xD;
&#xD;
      Temozolomide (TMZ), an orally administered drug, was shown to be efficient in DLGG, with a&#xD;
      good tolerance (Hoang-Xuan et al., 2004; Ricard et al., 2007). However, data regarding the&#xD;
      impact of TMZ on neuro-cognitive functioning and quality of life (QoL) are scarce. Only few&#xD;
      studies have performed an extensive, longitudinal assessment of cognition and QoL in DLGG&#xD;
      patients receiving TMZ (Liu et al., 2009; Blonski et al., 2012; Klein, 2015). Moreover, many&#xD;
      studies did not take into account the other factors that can alter the cognition such as the&#xD;
      tumor itself, the surgery, seizures, anti-epileptic drugs, but also the premorbid level of&#xD;
      cognition and the psychopathological affects such as depression, anxiety, or anger (Klein,&#xD;
      2015). To date, there is only few data on these psychopathological aspects in DLGG patients,&#xD;
      either at diagnosis or following chemotherapy or RT.&#xD;
&#xD;
      Studying QoL in patients DLGG receiving TMZ is complex because of the multiples interactions&#xD;
      between tumor characteristics, neurocognitive functioning, treatments, environment and&#xD;
      psychopathological context in which these patients experience symptoms. It is, however,&#xD;
      important to accurately evaluate these aspects in consideration of the young age, generally&#xD;
      preserved QoL at the time of diagnosis, possible implications of the disease on the&#xD;
      professional (DLGG patients are often still active), social and familial domain, and&#xD;
      relatively long survival of these patients. In the absence of a curative treatment for DLGG,&#xD;
      preserving patients' QoL is indeed a major goal.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 27, 2017</start_date>
  <completion_date type="Actual">December 31, 2021</completion_date>
  <primary_completion_date type="Actual">November 26, 2021</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>proportion of patients that consent to participate in the study</measure>
    <time_frame>through study completion, an average of 5 year</time_frame>
    <description>The participation rate: the proportion of patients that consent to participate in the study among the screened patients.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>proportion of included patients that will complete the evaluations at baseline, 6 months and 12 months</measure>
    <time_frame>through study completion, an average of 5 year</time_frame>
    <description>proportion of included patients that will complete the evaluations at baseline, 6 months and 12 months</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">26</enrollment>
  <condition>Glioma</condition>
  <arm_group>
    <arm_group_label>Temozolomide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment with TMZ will be given orally according to standard practices. The therapeutic schedule will be left at the investigator's discretion.&#xD;
Patients will be followed every 3 months during the treatment period, at the end of the treatment with TMZ, 6 months after the end of TMZ, and then annually until tumor progression.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Temozolomide</intervention_name>
    <description>Treatment with TMZ will be given orally according to standard practices. The therapeutic schedule will be left at the investigator's discretion.&#xD;
Patients will be followed every 3 months during the treatment period, at the end of the treatment with TMZ, 6 months after the end of TMZ, and then annually until tumor progression.</description>
    <arm_group_label>Temozolomide</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>QoL, neurocognitive and psycholpathological assessment</intervention_name>
    <description>This assessment will be performed at baseline, at 6 months, 12 months, 18 months, at the end of the treatment with TMZ, 6 months after the end of TMZ</description>
    <arm_group_label>Temozolomide</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult patient aged ≥ 18, no age limit;&#xD;
&#xD;
          -  Histologically-proven DLGG;&#xD;
&#xD;
          -  Patient receiving TMZ as a first line treatment after surgery, whatever the delay&#xD;
             between the surgery and the introduction of TMZ;&#xD;
&#xD;
          -  No previous oncologic treatment (except for surgery) for the DLGG;&#xD;
&#xD;
          -  Performance status (PS) score ≤ 2;&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) ≥ 1500 cells/µL and platelet count ≥ 100 000 cells/µL;&#xD;
&#xD;
          -  Total serum bilirubin concentration ≤ 1.5 x the upper limit of normal (ULN);&#xD;
&#xD;
          -  Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline&#xD;
             phosphatase ≤ 2.5 x the ULN;&#xD;
&#xD;
          -  Serum creatine concentration ≤ 1.5 x the ULN;&#xD;
&#xD;
          -  Negative pregnancy test in women of childbearing potential;&#xD;
&#xD;
          -  A signed informed consent obtained before any study specific procedures;&#xD;
&#xD;
          -  Patient fluent in French ;&#xD;
&#xD;
          -  Patient affiliated to a French social security system&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Anaplastic glioma (WHO grade III glioma);&#xD;
&#xD;
          -  Impaired neurocognitive functioning defined by a score &lt; 22 at the MoCA evaluation;&#xD;
&#xD;
          -  Visual or auditory deficit ;&#xD;
&#xD;
          -  Previous chemotherapy for the DLGG;&#xD;
&#xD;
          -  Previous RT for the DLGG;&#xD;
&#xD;
          -  Known hypersensitivity to any of the study drugs, or excipients in the formulation;&#xD;
&#xD;
          -  Hypersensitivity to dacarbazine (DTIC);&#xD;
&#xD;
          -  Severe myelosuppression;&#xD;
&#xD;
          -  Problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose&#xD;
             malabsorption;&#xD;
&#xD;
          -  Legal incapacity or physical, psychological social or geographical status interfering&#xD;
             with the patient's ability to sign the informed consent or to terminate the study;&#xD;
&#xD;
          -  Pregnant or breastfeeding women;&#xD;
&#xD;
          -  Men or women of childbearing potential who are unwilling to employ adequate&#xD;
             contraception, from the beginning of the study until 6 months after administration of&#xD;
             the last treatment dose;&#xD;
&#xD;
          -  Participation in another clinical trial with 30 prior to study entry.&#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>jean pierre bleuse</last_name>
    <role>Study Director</role>
    <affiliation>Institut régional du Cancer de Montpellier</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Institut regional du Cancer - Val d Aurelle</name>
      <address>
        <city>Montpellier</city>
        <zip>34298</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>August 16, 2017</study_first_submitted>
  <study_first_submitted_qc>August 18, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 22, 2017</study_first_posted>
  <last_update_submitted>January 7, 2022</last_update_submitted>
  <last_update_submitted_qc>January 7, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">January 11, 2022</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>Glioma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Temozolomide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03257618
org study id: ICM-URC2016-32
nct id: NCT03257618
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Studying QoL in patients DLGG receiving TMZ is complex because of the multiples interactions
      between tumor characteristics, neurocognitive functioning, treatments, environment and
      psychopathological context in which these patients experience symptoms. It is, however,
      important to accurately evaluate these aspects in consideration of the young age, generally
      preserved QoL at the time of diagnosis, possible implications of the disease on the
      professional (DLGG patients are often still active), social and familial domain, and
      relatively long survival of these patients. In the absence of a curative treatment for DLGG,
      preserving patients' QoL is indeed a major goal.
Diffuse low-grade gliomas (DLGG) (or WHO grade II gliomas, Louis et al., 2007) are rare
      tumors, with an incidence estimated at 1/105 person-year (Ostrom et al., 2015). They affect
      young people in their thirties or forties (Capelle et al., 2013). DLGG are characterized by a
      continuous growth and an unavoidable anaplastic transformation (Mandonnet et al., 2003).
      Epilepsy is the main presenting mode while neurological deficits are rare at diagnosis due to
      the brain plasticity allowed by the usually slow growth speed of these tumors. However,
      frequent alterations in cognitive functions (including mostly memory, executive functioning,
      and attention) have been described (Racine et al., 2015). The prognosis of DLGG is variable
      (Pignatti et al., 2002) and overall survival (OS) ranges from 5 years to 15 years according
      to several factors, including the tumor phenotype, the isocitrate dehydrogenase (IDH)
      mutation and the 1p19q codeletion, the tumor volume at diagnosis, and the tumor spontaneous
      growth speed (Capelle et al., 2013).

      The prognostic impact of the extent of surgery has now been well demonstrated (Jakola et al.,
      2012; Duffau 2016) and surgery is now the first treatment option (Soffietti et al., 2010). In
      unresectable DLGG or in patients with a progressive disease after surgery (with no
      possibility of a second surgery), several treatment options have been investigated, including
      radiation therapy (RT) and chemotherapy, but to date the timing and choice of treatment
      remains controversial. RT can be efficient in DLGG, however, the EORTC 22845 phase III trial
      found that early RT has no impact on OS compared to late RT, despite an increased
      progression-free survival (PFS) (van Den Bent et al., 2005). Moreover, some evidence of late
      decreased neurocognitive functioning has been consistently reported following RT (Klein et
      al., 2002; Douw et al., 2009). Because of this potential neurotoxicity and the absence of a
      benefit on OS of early RT, many neuro-oncological teams now only offer RT to patients with a
      progressive disease after chemotherapy.

      Temozolomide (TMZ), an orally administered drug, was shown to be efficient in DLGG, with a
      good tolerance (Hoang-Xuan et al., 2004; Ricard et al., 2007). However, data regarding the
      impact of TMZ on neuro-cognitive functioning and quality of life (QoL) are scarce. Only few
      studies have performed an extensive, longitudinal assessment of cognition and QoL in DLGG
      patients receiving TMZ (Liu et al., 2009; Blonski et al., 2012; Klein, 2015). Moreover, many
      studies did not take into account the other factors that can alter the cognition such as the
      tumor itself, the surgery, seizures, anti-epileptic drugs, but also the premorbid level of
      cognition and the psychopathological affects such as depression, anxiety, or anger (Klein,
      2015). To date, there is only few data on these psychopathological aspects in DLGG patients,
      either at diagnosis or following chemotherapy or RT.

      Studying QoL in patients DLGG receiving TMZ is complex because of the multiples interactions
      between tumor characteristics, neurocognitive functioning, treatments, environment and
      psychopathological context in which these patients experience symptoms. It is, however,
      important to accurately evaluate these aspects in consideration of the young age, generally
      preserved QoL at the time of diagnosis, possible implications of the disease on the
      professional (DLGG patients are often still active), social and familial domain, and
      relatively long survival of these patients. In the absence of a curative treatment for DLGG,
      preserving patients' QoL is indeed a major goal.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: proportion of patients that consent to participate in the study
time frame: through study completion, an average of 5 year
description: The participation rate: the proportion of patients that consent to participate in the study among the screened patients.
measure: proportion of included patients that will complete the evaluations at baseline, 6 months and 12 months
time frame: through study completion, an average of 5 year
description: proportion of included patients that will complete the evaluations at baseline, 6 months and 12 months
arm group label: Temozolomide
arm group type: Experimental
description: Treatment with TMZ will be given orally according to standard practices. The therapeutic schedule will be left at the investigator's discretion.
Patients will be followed every 3 months during the treatment period, at the end of the treatment with TMZ, 6 months after the end of TMZ, and then annually until tumor progression.
intervention type: Drug
intervention name: Temozolomide
description: Treatment with TMZ will be given orally according to standard practices. The therapeutic schedule will be left at the investigator's discretion.
Patients will be followed every 3 months during the treatment period, at the end of the treatment with TMZ, 6 months after the end of TMZ, and then annually until tumor progression.
arm group label: Temozolomide
intervention type: Other
intervention name: QoL, neurocognitive and psycholpathological assessment
description: This assessment will be performed at baseline, at 6 months, 12 months, 18 months, at the end of the treatment with TMZ, 6 months after the end of TMZ
arm group label: Temozolomide
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: jean pierre bleuse
role: Study Director
affiliation: Institut régional du Cancer de Montpellier
facility: 
country: France
responsible party type: Sponsor
mesh term: Glioma
mesh term: Temozolomide
sharing ipd: Undecided