<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/NCT01702610</url>
  </required_header>
  <id_info>
    <org_study_id>GEN-08-013</org_study_id>
    <secondary_id>MGRT01:TMZ/GBM</secondary_id>
    <nct_id>NCT01702610</nct_id>
  </id_info>
  <brief_title>Phase II Trial of Neo-adjuvant Temozolomide Prior to Combined Temozolomide and Concurrent Accelerated Hypofractionated External Beam Radiotherapy Followed by Adjuvant Temozolomide in Patients With Newly Diagnosed Glioblastoma Multiforme</brief_title>
  <sponsors>
    <lead_sponsor>
      <agency>McGill University Health Centre/Research Institute of the McGill University Health Centre</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>McGill University Health Centre/Research Institute of the McGill University Health Centre</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Patients with GBM, who were deemed ineligible for any active protocols at our centre,&#xD;
      received accelerated hypofractionation EBRT if 60Gy/20Fx using an IMRT technique with&#xD;
      conventional dose of concomitant and adjuvant TMX as per the STUPP's TMZ schedule. Thirty&#xD;
      five patients, 15 females and 20 males with a median age of 63 (range 31-78) were treated&#xD;
      with a median KPS of 90 (range 50-100). Four patients had multicentric disease at&#xD;
      presentation. Eight patients had biopsy only while the rest had a near total resection (n=14)&#xD;
      and partial resection (n=13) with a median follow-up of 12.1 months, the median survival was&#xD;
      14.4 months.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In this proposal, the total cumulative dose of TMZ is unchanged as compared to the doses used&#xD;
      in the Stupp protocol. In this proposal, the dose of TMZ is the same, with the sole&#xD;
      difference that TMZ will be given in a neo-adjuvant setting for two weeks and then continued&#xD;
      at the same dose concurrently with the accelerated hypofractionated EBRT delivering 60Gy in 4&#xD;
      weeks. The adjuvant component of TMZ remains unchanged from current standard practice.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>December 2008</start_date>
  <completion_date type="Actual">December 2014</completion_date>
  <primary_completion_date type="Actual">December 2014</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>Percent of patients completing the study treatment</measure>
    <time_frame>At one year</time_frame>
    <description>To determine overall survival.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>To assess toxicity of the regimen</measure>
    <time_frame>At one year</time_frame>
    <description>Toxicity will be assessed and graded according to CTCAE-V3</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">50</enrollment>
  <condition>Glioblastoma Mutliforme</condition>
  <arm_group>
    <arm_group_label>Temozolomide, Accelerated Hypofractionated RT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patient will receive two weeks of neo-adjuvant Temozolomide followed by Accelerated Hypofractionated RT for a total of 20 fractions for a total of 60Gy followed by Temozolomide for 12 cycles.</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>IMRT Technique</intervention_name>
    <arm_group_label>Temozolomide, Accelerated Hypofractionated RT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>IMRT and accelerated hypofractionation technique</intervention_name>
    <description>Intervention is the technique and accelerated fractionation used to treat GBM</description>
    <arm_group_label>Temozolomide, Accelerated Hypofractionated RT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>neo-adjuvant TMZ followed by accelerated hypofractionated EBRT</intervention_name>
    <description>Two weeks of neo-adjuvant TMZ followed by XRT+TMX followed by TMZ as adjuvant component</description>
    <arm_group_label>Temozolomide, Accelerated Hypofractionated RT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Temozolomide and Accelerated Hypofractionation RT</intervention_name>
    <arm_group_label>Temozolomide, Accelerated Hypofractionated RT</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age: 18 years or older&#xD;
&#xD;
          -  Histological confirmation of supratentorial GBM&#xD;
&#xD;
          -  KPS &gt; 60&#xD;
&#xD;
          -  Neurological function 0 or 1&#xD;
&#xD;
          -  Adequate bone marrow as defined below:&#xD;
&#xD;
          -  absolute neutrophil count (ANC) &gt; 1500 cells/mm3&#xD;
&#xD;
          -  platelets &gt; 100,000 cells/mm3&#xD;
&#xD;
          -  hemoglobin &gt; 10g/dl&#xD;
&#xD;
          -  Adequate renal function as defined below:&#xD;
&#xD;
          -  BUN &lt; 25mg/dl within 14 days prior to study registration&#xD;
&#xD;
          -  creatinine of 63 to 103 umol/L within 14 days prior to study registration&#xD;
&#xD;
          -  Adequate hepatic function as defined below:&#xD;
&#xD;
          -  Bilirubin of 3 to 21 umol/L within 14 days prior to study registration&#xD;
&#xD;
          -  ALT &amp; AST &lt; 3xnormal range within 14 days prior to study registration&#xD;
&#xD;
          -  Neoadjuvant TMZ to start within 3 weeks of surgery/biopsy if no resection was deemed&#xD;
             feasible&#xD;
&#xD;
          -  A diagnostic contrast-enhanced MRI or CT scan of the brain must be performed&#xD;
             preoperatively and postoperatively.&#xD;
&#xD;
          -  History, physical and neurological examination within 14 days prior to study&#xD;
             registration.&#xD;
&#xD;
          -  For females of child-bearing potential, negative pregnancy test within 72 hours prior&#xD;
             to starting TMZ.&#xD;
&#xD;
          -  Able to sign an informed study-specific consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Margin of contrast-enhanced residual mass closer than 15mm from the optic chiasm or&#xD;
             optic nerves.&#xD;
&#xD;
          -  Prior invasive malignancy, unless disease-free for &gt;3years&#xD;
&#xD;
          -  Recurrent or multifocal GBM&#xD;
&#xD;
          -  Severe co-morbidities such as&#xD;
&#xD;
          -  unstable angina&#xD;
&#xD;
          -  transmural myocardial infarction within 6 months&#xD;
&#xD;
          -  COPD at the time of registration&#xD;
&#xD;
          -  Hepatic insufficiency&#xD;
&#xD;
          -  Bacterial or fungal infection requiring IV antibiotics at the time of registration&#xD;
&#xD;
          -  Acquired Immune Deficiency Syndrome (AIDS)&#xD;
&#xD;
          -  Major medical illnesses or psychiatric impairments&#xD;
&#xD;
          -  Pregnant women or lactating women&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>McGill University Health Center</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H3G 1A4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>September 2016</verification_date>
  <study_first_submitted>August 22, 2012</study_first_submitted>
  <study_first_submitted_qc>October 4, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 8, 2012</study_first_posted>
  <last_update_submitted>September 26, 2016</last_update_submitted>
  <last_update_submitted_qc>September 26, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 28, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>McGill University Health Centre/Research Institute of the McGill University Health Centre</investigator_affiliation>
    <investigator_full_name>George Shenouda</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glioblastoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Temozolomide</mesh_term>
  </intervention_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/NCT01702610
org study id: GEN-08-013
secondary id: MGRT01:TMZ/GBM
nct id: NCT01702610
lead sponsor: 
has dmc: No
Patients with GBM, who were deemed ineligible for any active protocols at our centre,
      received accelerated hypofractionation EBRT if 60Gy/20Fx using an IMRT technique with
      conventional dose of concomitant and adjuvant TMX as per the STUPP's TMZ schedule. Thirty
      five patients, 15 females and 20 males with a median age of 63 (range 31-78) were treated
      with a median KPS of 90 (range 50-100). Four patients had multicentric disease at
      presentation. Eight patients had biopsy only while the rest had a near total resection (n=14)
      and partial resection (n=13) with a median follow-up of 12.1 months, the median survival was
      14.4 months.
In this proposal, the total cumulative dose of TMZ is unchanged as compared to the doses used
      in the Stupp protocol. In this proposal, the dose of TMZ is the same, with the sole
      difference that TMZ will be given in a neo-adjuvant setting for two weeks and then continued
      at the same dose concurrently with the accelerated hypofractionated EBRT delivering 60Gy in 4
      weeks. The adjuvant component of TMZ remains unchanged from current standard practice.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percent of patients completing the study treatment
time frame: At one year
description: To determine overall survival.
measure: To assess toxicity of the regimen
time frame: At one year
description: Toxicity will be assessed and graded according to CTCAE-V3
arm group label: Temozolomide, Accelerated Hypofractionated RT
arm group type: Experimental
description: Patient will receive two weeks of neo-adjuvant Temozolomide followed by Accelerated Hypofractionated RT for a total of 20 fractions for a total of 60Gy followed by Temozolomide for 12 cycles.
intervention type: Radiation
intervention name: IMRT Technique
arm group label: Temozolomide, Accelerated Hypofractionated RT
intervention type: Radiation
intervention name: IMRT and accelerated hypofractionation technique
description: Intervention is the technique and accelerated fractionation used to treat GBM
arm group label: Temozolomide, Accelerated Hypofractionated RT
intervention type: Radiation
intervention name: neo-adjuvant TMZ followed by accelerated hypofractionated EBRT
description: Two weeks of neo-adjuvant TMZ followed by XRT+TMX followed by TMZ as adjuvant component
arm group label: Temozolomide, Accelerated Hypofractionated RT
intervention type: Drug
intervention name: Temozolomide and Accelerated Hypofractionation RT
arm group label: Temozolomide, Accelerated Hypofractionated RT
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: McGill University Health Centre/Research Institute of the McGill University Health Centre
investigator full name: George Shenouda
investigator title: Principal Investigator
mesh term: Glioblastoma
mesh term: Temozolomide