<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/NCT02209948</url>
  </required_header>
  <id_info>
    <org_study_id>GEINO 14-01</org_study_id>
    <secondary_id>2014-000838-39</secondary_id>
    <nct_id>NCT02209948</nct_id>
  </id_info>
  <brief_title>Temozolomide 12 Cycles Versus 6 Cycles of Standard First-line Treatment in Patients With Glioblastoma.</brief_title>
  <official_title>Clinical Trial Phase IIB Randomized, Multicenter, of Continuation or Non Continuation With 6 Cycles of Temozolomide After the First 6 Cycles of Standard First-line Treatment in Patients With Glioblastoma.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Grupo Español de Investigación en Neurooncología</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Grupo Español de Investigación en Neurooncología</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to show if prolonging treatment with temozolomide to 12 cycles&#xD;
      improve progression-free survival in patients with glioblastoma included in this study,&#xD;
      randomized according to o6-methylguanine-DNA-methyltransferase (MGMT) methylation status and&#xD;
      residual disease or not, to receive an additional 6 cycles of temozolomide.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 22, 2014</start_date>
  <completion_date type="Actual">June 14, 2019</completion_date>
  <primary_completion_date type="Actual">June 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression Free Survival at 6 Month</measure>
    <time_frame>6 month</time_frame>
    <description>Percentage of patients without progression of disease and time between start of treatment and progression of disease.&#xD;
The progression disease is defined as the time from the date of randomization to the date of progression defined according to the RANO criteria.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Adverse Effects</measure>
    <time_frame>Through the whole study. 4 years</time_frame>
    <description>Total number of patients presenting adverse events, stratified by type of event and grade. Adverse Events of special interest: Only relevant differences in toxicity by arm.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progresion Free Survival Median Values</measure>
    <time_frame>Through the whole study. 4 years. The median follow up for each patient was 33.4 months</time_frame>
    <description>It will be measured following Response assessment in neuro-oncology (RANO) guidelines: progression-free survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>Through the whole study. 4 years. The median follow up for each patient was 33.4 months</time_frame>
    <description>Time between start of treatment and death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median Progression-free Survival (PFS) by Arm and MGMT Methylation Status</measure>
    <time_frame>Through the whole study. 4 years. The median follow up for each patient was 33.4 months</time_frame>
    <description>Median Progression Free Survival depending on treatment arm in patients with MGMT methylation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median Overall Survival (OS) by Arm and MGMT Methylation Status</measure>
    <time_frame>Through the whole study. 4 years. The median follow up for each patient was 33.4 months</time_frame>
    <description>Median OS depending on treatment arm in patients with methylated MGMT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Translational Sub-study - Biomarkers: mutS Homolog 6 (MSH6) Immunoreactivity</measure>
    <time_frame>baseline</time_frame>
    <description>partial immunoreactivity of MSH6 in patients by treatment arm. Tumor samples were stained by immuno-histochemical techniques.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">166</enrollment>
  <condition>Glioblastoma</condition>
  <arm_group>
    <arm_group_label>Temozolomide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Those patients will take 6 additional Temozolomide cycles</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Without treatment</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Temozolomide</intervention_name>
    <arm_group_label>Temozolomide</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Ability to understand and sign the informed consent document .&#xD;
&#xD;
          2. Age greater than or equal 18.&#xD;
&#xD;
          3. Patients with glioblastoma according to WHO classification (glioblastoma ) who&#xD;
             received chemo- radiotherapy and temozolomide -based chemotherapy ( Stupp scheme ) and&#xD;
             have completed 6 cycles of adjuvant temozolomide (with or without bevacizumab) in the&#xD;
             context of standard treatment without presenting progression of disease.&#xD;
&#xD;
          4. Availability of tumor tissue from the first surgery for centralized histological&#xD;
             review , for determining the MGMT study if you have not done in the center of origin.&#xD;
             (If they were made in the center of origin the result of the center will be accepted&#xD;
             ).&#xD;
&#xD;
          5. Stable dose of dexamethasone in the inclusion never above corticoids dose received in&#xD;
             cycle 6 of the adjuvant .&#xD;
&#xD;
          6. Index greater than or equal 60 % Karnofsky.&#xD;
&#xD;
          7. All patients must show no progression of disease in a brain nuclear magnetic resonance&#xD;
             (NMR) as defined in RANO established criteria before randomization .&#xD;
&#xD;
          8. Basal NMR study on a maximum of 6 weeks prior to inclusion, in which no progress is&#xD;
             observed and is permitted to manage the care 6th cycle ( NMR performed after the 6th&#xD;
             cycle of adjuvant is also acceptable as long as no progression was observed).&#xD;
&#xD;
          9. Adequate bone marrow reserve : hematocrit greater or equal 29% , white blood cell&gt;&#xD;
             3,000 , RAN greater or equal 1,500 cells / ul , platelets greater or equal 100,000&#xD;
             cells / ul.&#xD;
&#xD;
         10. Creatinine &lt;1.5 times the upper limit of normal (ULN) of the laboratory performing the&#xD;
             analysis.&#xD;
&#xD;
         11. Serum bilirubin &lt;1.5 / ULN; SGOT , SGPT &lt; 2.5 times the upper limit of normal of the&#xD;
             laboratory performing the analysis. Serum &lt; 3/ULN alkaline phosphatases .&#xD;
&#xD;
         12. Effective contraceptive method in patients and their partners.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Less than 5 years of any previous invasive neoplasia. In situ cervical carcinoma or&#xD;
             basal cell skin carcinoma accepted.&#xD;
&#xD;
          2. Concomitant treatment with other investigational agents (other concomitant&#xD;
             bevacizumab) .&#xD;
&#xD;
          3. Presence of any clinically significant gastrointestinal abnormalities that may affect&#xD;
             the decision , transit or absorption of study drug , such as the inability to take&#xD;
             medication in tablets by mouth.&#xD;
&#xD;
          4. Presence of any psychiatric or cognitive disorder that limits understanding or written&#xD;
             informed consent and / or impair compliance with the requirements of this protocol.&#xD;
&#xD;
          5. Concurrent disease that prevents the continuation of temozolomide treatment.&#xD;
&#xD;
          6. Presence of leptomeningeal dissemination.&#xD;
&#xD;
          7. Pregnant or breastfeeding.&#xD;
&#xD;
          8. Positive patients receiving combination antiretroviral therapy in HIV&#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>Carmen Balañá, M.D.</last_name>
    <role>Study Chair</role>
    <affiliation>Hospital Germans Trias i Pujol - ICO Badalona</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Mª Ángeles Vaz, M.D.</last_name>
    <role>Study Chair</role>
    <affiliation>Hospital Universitario Ramon y Cajal</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital Universitari Germans Trias i Pujol/ICO Badalona</name>
      <address>
        <city>Badalona</city>
        <state>Barcelona</state>
        <zip>08916</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Català d'Oncologia L'Hospitalet</name>
      <address>
        <city>L'Hospitalet de Llobregat</city>
        <state>Barcelona</state>
        <zip>08908</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Fundación Alcorcón</name>
      <address>
        <city>Alcorcón</city>
        <state>Madrid</state>
        <zip>28922</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Son Espases</name>
      <address>
        <city>Palma de Mallorca</city>
        <state>Mallorca</state>
        <zip>07010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Sant Joan de Reus</name>
      <address>
        <city>Reus</city>
        <state>Tarragona</state>
        <zip>43204</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Consorcio Hospitalario Provincial de Castellón</name>
      <address>
        <city>Castelló</city>
        <state>Valencia</state>
        <zip>12002</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital del Mar</name>
      <address>
        <city>Barcelona</city>
        <zip>08003</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de la Santa Creu i Sant Pau</name>
      <address>
        <city>Barcelona</city>
        <zip>08025</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clínic de Barcelona</name>
      <address>
        <city>Barcelona</city>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital General de Ciudad Real</name>
      <address>
        <city>Ciudad Real</city>
        <zip>13005</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Dr. Josep Trueta de Girona</name>
      <address>
        <city>Girona</city>
        <zip>17007</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Arnau de Vilanova</name>
      <address>
        <city>Lleida</city>
        <zip>25198</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Lucus Augusti</name>
      <address>
        <city>Lugo</city>
        <zip>27003</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Ramón y Cajal</name>
      <address>
        <city>Madrid</city>
        <zip>28034</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Clínico San Carlos</name>
      <address>
        <city>Madrid</city>
        <zip>28040</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario 12 de Octubre</name>
      <address>
        <city>Madrid</city>
        <zip>28041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clínico Universitario de Salamanca</name>
      <address>
        <city>Salamanca</city>
        <zip>37007</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen del Rocío</name>
      <address>
        <city>Sevilla</city>
        <zip>41013</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Consorcio Hospital General Universitario de Valencia</name>
      <address>
        <city>Valencia</city>
        <zip>46014</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Miguel Servet</name>
      <address>
        <city>Zaragoza</city>
        <zip>50009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>August 4, 2014</study_first_submitted>
  <study_first_submitted_qc>August 5, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 6, 2014</study_first_posted>
  <results_first_submitted>October 20, 2020</results_first_submitted>
  <results_first_submitted_qc>December 17, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">January 12, 2021</results_first_posted>
  <last_update_submitted>December 17, 2020</last_update_submitted>
  <last_update_submitted_qc>December 17, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 12, 2021</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>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>
  <provided_document_section>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>May 1, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/48/NCT02209948/SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>September 8, 2014</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/48/NCT02209948/Prot_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>7 patients do not meet inclusion criteria. Only 159 patients were randomized</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Temozolomide</title>
          <description>Temozolomide dose 150/200 mg/m2/d for 5 days every 28 days for 6 cycles (total 12 cycles of adjuvant temozolomide).</description>
        </group>
        <group group_id="P2">
          <title>Without Treatment</title>
          <description>No treatment (total 6 cycles of adjuvant Temozolomide).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="80"/>
                <participants group_id="P2" count="79"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Recieved Alocated Intervention</title>
              <participants_list>
                <participants group_id="P1" count="80"/>
                <participants group_id="P2" count="79"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Lost to Follow up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Discontinued Due to Progression</title>
              <participants_list>
                <participants group_id="P1" count="31"/>
                <participants group_id="P2" count="39"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="80"/>
                <participants group_id="P2" count="79"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Temozolomide</title>
          <description>Temozolomide dose 150/200 mg/m2/d for 5 days every 28 days for 6 cycles (total 12 cycles of adjuvant temozolomide).</description>
        </group>
        <group group_id="B2">
          <title>Without Treatment</title>
          <description>No treatment (total 6 cycles of adjuvant Temozolomide).</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="80"/>
            <count group_id="B2" value="79"/>
            <count group_id="B3" value="159"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="80"/>
                    <count group_id="B2" value="79"/>
                    <count group_id="B3" value="159"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="60.7" lower_limit="31" upper_limit="79"/>
                    <measurement group_id="B2" value="60.4" lower_limit="29" upper_limit="83"/>
                    <measurement group_id="B3" value="60.4" lower_limit="29" upper_limit="83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="80"/>
                    <count group_id="B2" value="79"/>
                    <count group_id="B3" value="159"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="38"/>
                    <measurement group_id="B2" value="38"/>
                    <measurement group_id="B3" value="76"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="42"/>
                    <measurement group_id="B2" value="41"/>
                    <measurement group_id="B3" value="83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Spain</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="80"/>
                    <count group_id="B2" value="79"/>
                    <count group_id="B3" value="159"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="80"/>
                    <measurement group_id="B2" value="79"/>
                    <measurement group_id="B3" value="159"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Residual disease (&gt;10mm)</title>
          <description>The presence of residual disease (visible on MRI and with at least one lesion bigger than 10mm) at the time of inclusion.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="80"/>
                    <count group_id="B2" value="79"/>
                    <count group_id="B3" value="159"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Yes</title>
                  <measurement_list>
                    <measurement group_id="B1" value="41"/>
                    <measurement group_id="B2" value="42"/>
                    <measurement group_id="B3" value="83"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No</title>
                  <measurement_list>
                    <measurement group_id="B1" value="39"/>
                    <measurement group_id="B2" value="37"/>
                    <measurement group_id="B3" value="76"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Karnofski Performance Status (KPS) index</title>
          <description>KPS measures the ability of cancer patients to perform routine tasks. Scores on the KPS range from 0% to 100%. A higher score means that the patient is better able to perform daily activities.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="80"/>
                    <count group_id="B2" value="79"/>
                    <count group_id="B3" value="159"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>&lt;70%</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=70%</title>
                  <measurement_list>
                    <measurement group_id="B1" value="78"/>
                    <measurement group_id="B2" value="77"/>
                    <measurement group_id="B3" value="155"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Residual Neurological symptom</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="80"/>
                    <count group_id="B2" value="79"/>
                    <count group_id="B3" value="159"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Yes</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="27"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No</title>
                  <measurement_list>
                    <measurement group_id="B1" value="60"/>
                    <measurement group_id="B2" value="71"/>
                    <measurement group_id="B3" value="131"/>
                  </measurement_list>
                </category>
                <category>
                  <title>NA</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Dexamethasone (DXM) dose at inclusion</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="80"/>
                    <count group_id="B2" value="79"/>
                    <count group_id="B3" value="159"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>0 mg</title>
                  <measurement_list>
                    <measurement group_id="B1" value="67"/>
                    <measurement group_id="B2" value="70"/>
                    <measurement group_id="B3" value="137"/>
                  </measurement_list>
                </category>
                <category>
                  <title>0.5-2 mg</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;2 mg</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Barthel index</title>
          <description>Barthel index measures functional independence and residual disability in activities of daily living. Values range from 0 to 5, with lower values indicating more disability.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="80"/>
                    <count group_id="B2" value="79"/>
                    <count group_id="B3" value="159"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>0</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>1</title>
                  <measurement_list>
                    <measurement group_id="B1" value="68"/>
                    <measurement group_id="B2" value="70"/>
                    <measurement group_id="B3" value="138"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Mini-mental status examinaion (MMSE)</title>
          <description>The test evaluates attention, language, memory, orientation, visuospatial proficiency.&#xD;
The Mini-mental state examination is scored on a scale of 0-30 with scores &gt; 27 interpreted as normal cognitive status. The lower values are associated to worse cognitive status.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="80"/>
                    <count group_id="B2" value="79"/>
                    <count group_id="B3" value="159"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>&lt;27</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="26"/>
                  </measurement_list>
                </category>
                <category>
                  <title>≥27</title>
                  <measurement_list>
                    <measurement group_id="B1" value="51"/>
                    <measurement group_id="B2" value="60"/>
                    <measurement group_id="B3" value="111"/>
                  </measurement_list>
                </category>
                <category>
                  <title>NP/ND</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Anticonvulsant therapy</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="80"/>
                    <count group_id="B2" value="79"/>
                    <count group_id="B3" value="159"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Yes</title>
                  <measurement_list>
                    <measurement group_id="B1" value="37"/>
                    <measurement group_id="B2" value="38"/>
                    <measurement group_id="B3" value="75"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No</title>
                  <measurement_list>
                    <measurement group_id="B1" value="43"/>
                    <measurement group_id="B2" value="41"/>
                    <measurement group_id="B3" value="84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Initial surgery- Treatment at diagnosis.</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="80"/>
                    <count group_id="B2" value="79"/>
                    <count group_id="B3" value="159"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Biopsy</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="17"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Complete resection by post-op MRI)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                    <measurement group_id="B2" value="35"/>
                    <measurement group_id="B3" value="63"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Complete resection without post-op MRI</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="34"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Subtotal resection</title>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>O6-methylguanine DNA methyltransferase (MGMT) Methylation status</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="80"/>
                    <count group_id="B2" value="79"/>
                    <count group_id="B3" value="159"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Methylated</title>
                  <measurement_list>
                    <measurement group_id="B1" value="49"/>
                    <measurement group_id="B2" value="48"/>
                    <measurement group_id="B3" value="97"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unmethylated</title>
                  <measurement_list>
                    <measurement group_id="B1" value="31"/>
                    <measurement group_id="B2" value="31"/>
                    <measurement group_id="B3" value="62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Isocitrate dehydrogenase 1 (IDH1) Mutation status</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="80"/>
                    <count group_id="B2" value="79"/>
                    <count group_id="B3" value="159"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>IDH1-R132 mutated by ICH</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>IDH1-R132 non mutated by ICH</title>
                  <measurement_list>
                    <measurement group_id="B1" value="71"/>
                    <measurement group_id="B2" value="66"/>
                    <measurement group_id="B3" value="137"/>
                  </measurement_list>
                </category>
                <category>
                  <title>not determined</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Progression Free Survival at 6 Month</title>
        <description>Percentage of patients without progression of disease and time between start of treatment and progression of disease.&#xD;
The progression disease is defined as the time from the date of randomization to the date of progression defined according to the RANO criteria.</description>
        <time_frame>6 month</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Temozolomide</title>
            <description>Temozolomide dose 150/200 mg/m2/d for 5 days every 28 days for 6 cycles (total 12 cycles of adjuvant temozolomide).</description>
          </group>
          <group group_id="O2">
            <title>Without Treatment</title>
            <description>No treatment (total 6 cycles of adjuvant Temozolomide).</description>
          </group>
        </group_list>
        <measure>
          <title>Progression Free Survival at 6 Month</title>
          <description>Percentage of patients without progression of disease and time between start of treatment and progression of disease.&#xD;
The progression disease is defined as the time from the date of randomization to the date of progression defined according to the RANO criteria.</description>
          <units>percentage of patients</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="80"/>
                <count group_id="O2" value="79"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="61.3" lower_limit="51.5" upper_limit="72.9"/>
                    <measurement group_id="O2" value="55.7" lower_limit="45.8" upper_limit="67.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Adverse Effects</title>
        <description>Total number of patients presenting adverse events, stratified by type of event and grade. Adverse Events of special interest: Only relevant differences in toxicity by arm.</description>
        <time_frame>Through the whole study. 4 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Temozolomide</title>
            <description>Temozolomide dose 150/200 mg/m2/d for 5 days every 28 days for 6 cycles (total 12 cycles of adjuvant temozolomide).</description>
          </group>
          <group group_id="O2">
            <title>Without Treatment</title>
            <description>No treatment (total 6 cycles of adjuvant Temozolomide).</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Adverse Effects</title>
          <description>Total number of patients presenting adverse events, stratified by type of event and grade. Adverse Events of special interest: Only relevant differences in toxicity by arm.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="80"/>
                <count group_id="O2" value="79"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Lymphopenia</title>
              <category_list>
                <category>
                  <title>Grade 1-2</title>
                  <measurement_list>
                    <measurement group_id="O1" value="52"/>
                    <measurement group_id="O2" value="33"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Grade 3-4</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>not affected</title>
                  <measurement_list>
                    <measurement group_id="O1" value="25"/>
                    <measurement group_id="O2" value="46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Thrombocytopenia</title>
              <category_list>
                <category>
                  <title>Grade 1-2</title>
                  <measurement_list>
                    <measurement group_id="O1" value="36"/>
                    <measurement group_id="O2" value="17"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Grade 3-4</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>not affected</title>
                  <measurement_list>
                    <measurement group_id="O1" value="42"/>
                    <measurement group_id="O2" value="62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nausea and vomiting</title>
              <category_list>
                <category>
                  <title>Grade 1-2</title>
                  <measurement_list>
                    <measurement group_id="O1" value="30"/>
                    <measurement group_id="O2" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Grade 3-4</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>not affected</title>
                  <measurement_list>
                    <measurement group_id="O1" value="50"/>
                    <measurement group_id="O2" value="69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Fatigue</title>
              <category_list>
                <category>
                  <title>Grade 1-2</title>
                  <measurement_list>
                    <measurement group_id="O1" value="35"/>
                    <measurement group_id="O2" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Grade 3-4</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>not affected</title>
                  <measurement_list>
                    <measurement group_id="O1" value="45"/>
                    <measurement group_id="O2" value="58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Leucopenia</title>
              <category_list>
                <category>
                  <title>Grade 1-2</title>
                  <measurement_list>
                    <measurement group_id="O1" value="29"/>
                    <measurement group_id="O2" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Grade 3-4</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>not affected</title>
                  <measurement_list>
                    <measurement group_id="O1" value="50"/>
                    <measurement group_id="O2" value="59"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progresion Free Survival Median Values</title>
        <description>It will be measured following Response assessment in neuro-oncology (RANO) guidelines: progression-free survival</description>
        <time_frame>Through the whole study. 4 years. The median follow up for each patient was 33.4 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Temozolomide</title>
            <description>Temozolomide dose 150/200 mg/m2/d for 5 days every 28 days for 6 cycles (total 12 cycles of adjuvant temozolomide).</description>
          </group>
          <group group_id="O2">
            <title>Without Treatment</title>
            <description>No treatment (total 6 cycles of adjuvant Temozolomide).</description>
          </group>
        </group_list>
        <measure>
          <title>Progresion Free Survival Median Values</title>
          <description>It will be measured following Response assessment in neuro-oncology (RANO) guidelines: progression-free survival</description>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="80"/>
                <count group_id="O2" value="79"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.5" lower_limit="5.93" upper_limit="13.07"/>
                    <measurement group_id="O2" value="7.77" lower_limit="5.70" upper_limit="9.83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Log Rank (Mantel-Cox)</non_inferiority_desc>
            <p_value>0.943</p_value>
            <p_value_desc>Threshold P-value of 0.05</p_value_desc>
            <method>Log Rank</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival</title>
        <description>Time between start of treatment and death</description>
        <time_frame>Through the whole study. 4 years. The median follow up for each patient was 33.4 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Temozolomide</title>
            <description>Temozolomide dose 150/200 mg/m2/d for 5 days every 28 days for 6 cycles (total 12 cycles of adjuvant temozolomide).</description>
          </group>
          <group group_id="O2">
            <title>Without Treatment</title>
            <description>No treatment (total 6 cycles of adjuvant Temozolomide).</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival</title>
          <description>Time between start of treatment and death</description>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="80"/>
                <count group_id="O2" value="79"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.2" lower_limit="16.7" upper_limit="23.8"/>
                    <measurement group_id="O2" value="23.3" lower_limit="17.9" upper_limit="28.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.16</p_value>
            <p_value_desc>Threshold of significance P-value 0.05</p_value_desc>
            <method>Regression, Cox</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.30</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.90</ci_lower_limit>
            <ci_upper_limit>1.88</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Median Progression-free Survival (PFS) by Arm and MGMT Methylation Status</title>
        <description>Median Progression Free Survival depending on treatment arm in patients with MGMT methylation</description>
        <time_frame>Through the whole study. 4 years. The median follow up for each patient was 33.4 months</time_frame>
        <population>Patients with MGMT methylation</population>
        <group_list>
          <group group_id="O1">
            <title>Temozolomide</title>
            <description>Temozolomide dose 150/200 mg/m2/d for 5 days every 28 days for 6 cycles (total 12 cycles of adjuvant temozolomide).</description>
          </group>
          <group group_id="O2">
            <title>Without Treatment</title>
            <description>No treatment (total 6 cycles of adjuvant Temozolomide).</description>
          </group>
        </group_list>
        <measure>
          <title>Median Progression-free Survival (PFS) by Arm and MGMT Methylation Status</title>
          <description>Median Progression Free Survival depending on treatment arm in patients with MGMT methylation</description>
          <population>Patients with MGMT methylation</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="49"/>
                <count group_id="O2" value="48"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.4" lower_limit="9.2" upper_limit="13.6"/>
                    <measurement group_id="O2" value="8.5" lower_limit="6.5" upper_limit="10.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.99</p_value>
            <p_value_desc>Threshold for significance P-value 0.05</p_value_desc>
            <method>Regression, Cox</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.65</ci_lower_limit>
            <ci_upper_limit>1.5</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Median Overall Survival (OS) by Arm and MGMT Methylation Status</title>
        <description>Median OS depending on treatment arm in patients with methylated MGMT</description>
        <time_frame>Through the whole study. 4 years. The median follow up for each patient was 33.4 months</time_frame>
        <population>Patients with MGMT methylation</population>
        <group_list>
          <group group_id="O1">
            <title>Temozolomide</title>
            <description>Temozolomide dose 150/200 mg/m2/d for 5 days every 28 days for 6 cycles (total 12 cycles of adjuvant temozolomide).</description>
          </group>
          <group group_id="O2">
            <title>Without Treatment</title>
            <description>No treatment (total 6 cycles of adjuvant Temozolomide).</description>
          </group>
        </group_list>
        <measure>
          <title>Median Overall Survival (OS) by Arm and MGMT Methylation Status</title>
          <description>Median OS depending on treatment arm in patients with methylated MGMT</description>
          <population>Patients with MGMT methylation</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="49"/>
                <count group_id="O2" value="48"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20.7" lower_limit="14.7" upper_limit="26.7"/>
                    <measurement group_id="O2" value="27.1" lower_limit="20.3" upper_limit="33.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.13</p_value>
            <p_value_desc>threshold for significance 0.05</p_value_desc>
            <method>Regression, Cox</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.45</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.89</ci_lower_limit>
            <ci_upper_limit>2.33</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Translational Sub-study - Biomarkers: mutS Homolog 6 (MSH6) Immunoreactivity</title>
        <description>partial immunoreactivity of MSH6 in patients by treatment arm. Tumor samples were stained by immuno-histochemical techniques.</description>
        <time_frame>baseline</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Temozolomide</title>
            <description>Temozolomide dose 150/200 mg/m2/d for 5 days every 28 days for 6 cycles (total 12 cycles of adjuvant temozolomide).</description>
          </group>
          <group group_id="O2">
            <title>Without Treatment</title>
            <description>No treatment (total 6 cycles of adjuvant Temozolomide).</description>
          </group>
        </group_list>
        <measure>
          <title>Translational Sub-study - Biomarkers: mutS Homolog 6 (MSH6) Immunoreactivity</title>
          <description>partial immunoreactivity of MSH6 in patients by treatment arm. Tumor samples were stained by immuno-histochemical techniques.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="80"/>
                <count group_id="O2" value="79"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>MSH6 partial immunoreactivity</title>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>no MSH6 partial immunoreactivity</title>
                  <measurement_list>
                    <measurement group_id="O1" value="75"/>
                    <measurement group_id="O2" value="73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Through the clinical study. About 4 years</time_frame>
      <desc>In addition, clinically relevant changes on physical examination and abnormal parameters found on complementary examinations (eg radiography, ECG) should also be reported like Adverse Event (AE).</desc>
      <group_list>
        <group group_id="E1">
          <title>Temozolomide</title>
          <description>Temozolomide dose 150/200 mg/m2/d for 5 days every 28 days for 6 cycles (total 12 cycles of adjuvant temozolomide).</description>
        </group>
        <group group_id="E2">
          <title>Without Treatment</title>
          <description>No treatment (total 6 cycles of adjuvant Temozolomide).</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>NCI CTCAE version 4</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="63" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="52" subjects_at_risk="79"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="79"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Claudication</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="79"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="80"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="79"/>
              </event>
              <event>
                <sub_title>General deterioration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="80"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="79"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Respiratory infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="79"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Femur fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="79"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dysarthria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="80"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="79"/>
              </event>
              <event>
                <sub_title>Neurological impairment</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="79"/>
              </event>
              <event>
                <sub_title>Epileptic crisis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="79"/>
              </event>
              <event>
                <sub_title>Seizure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="79"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="80"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="79"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Intracraneal hypertension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="79"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="80"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="79"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>1</frequency_threshold>
        <default_vocab>NCI CTCAE version 4</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="80" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="79" subjects_at_risk="79"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" events="30" subjects_affected="30" subjects_at_risk="80"/>
                <counts group_id="E2" events="20" subjects_affected="20" subjects_at_risk="79"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="80"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="79"/>
              </event>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="80"/>
                <counts group_id="E2" events="8" subjects_affected="8" subjects_at_risk="79"/>
              </event>
              <event>
                <sub_title>Lymphopenia</sub_title>
                <counts group_id="E1" events="55" subjects_affected="55" subjects_at_risk="80"/>
                <counts group_id="E2" events="33" subjects_affected="33" subjects_at_risk="79"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" events="38" subjects_affected="38" subjects_at_risk="80"/>
                <counts group_id="E2" events="17" subjects_affected="17" subjects_at_risk="79"/>
              </event>
              <event>
                <sub_title>Alkaline Phosphatase High</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="80"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="79"/>
              </event>
              <event>
                <sub_title>Potasium High</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="80"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="79"/>
              </event>
              <event>
                <sub_title>Sodium High</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="80"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="79"/>
              </event>
              <event>
                <sub_title>GGT High</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="80"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="79"/>
              </event>
              <event>
                <sub_title>GOT High</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="80"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="79"/>
              </event>
              <event>
                <sub_title>GPT High</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="80"/>
                <counts group_id="E2" events="7" subjects_affected="7" subjects_at_risk="79"/>
              </event>
              <event>
                <sub_title>Bilirubin High</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="80"/>
                <counts group_id="E2" events="8" subjects_affected="8" subjects_at_risk="79"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac Events</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="80"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="79"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Hearing loss</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="80"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="79"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea and Vomiting</sub_title>
                <counts group_id="E1" events="30" subjects_affected="30" subjects_at_risk="80"/>
                <counts group_id="E2" events="10" subjects_affected="10" subjects_at_risk="79"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" events="35" subjects_affected="35" subjects_at_risk="80"/>
                <counts group_id="E2" events="21" subjects_affected="21" subjects_at_risk="79"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="13" subjects_affected="13" subjects_at_risk="80"/>
                <counts group_id="E2" events="10" subjects_affected="10" subjects_at_risk="79"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="80"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="79"/>
              </event>
              <event>
                <sub_title>Infection</sub_title>
                <counts group_id="E1" events="11" subjects_affected="11" subjects_at_risk="80"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="79"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperglicemia</sub_title>
                <counts group_id="E1" events="14" subjects_affected="14" subjects_at_risk="80"/>
                <counts group_id="E2" events="19" subjects_affected="19" subjects_at_risk="79"/>
              </event>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="80"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="79"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Bone Events</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="80"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="79"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Neurologic</sub_title>
                <counts group_id="E1" events="38" subjects_affected="38" subjects_at_risk="80"/>
                <counts group_id="E2" events="41" subjects_affected="41" subjects_at_risk="79"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="80"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="79"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Creatinine high</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="80"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="79"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Respiratory disorders</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="80"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="79"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Skin disorders</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="80"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="79"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Thromboembolism</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="80"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="79"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Our trial was not powered to detect significant differences in PFS or OS. To do so, we would have had to know the survival distribution for patients who complete the standard six cycles without progression, but this information was not available</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Pau Doñate</name_or_title>
      <organization>MFAR Clinical Research</organization>
      <phone>0034934344412</phone>
      <email>investigacion@mfar.net</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02209948
org study id: GEINO 14-01
secondary id: 2014-000838-39
nct id: NCT02209948
lead sponsor: 
has dmc: No
The purpose of this study is to show if prolonging treatment with temozolomide to 12 cycles
      improve progression-free survival in patients with glioblastoma included in this study,
      randomized according to o6-methylguanine-DNA-methyltransferase (MGMT) methylation status and
      residual disease or not, to receive an additional 6 cycles of temozolomide.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression Free Survival at 6 Month
time frame: 6 month
description: Percentage of patients without progression of disease and time between start of treatment and progression of disease.
The progression disease is defined as the time from the date of randomization to the date of progression defined according to the RANO criteria.
measure: Number of Participants With Adverse Effects
time frame: Through the whole study. 4 years
description: Total number of patients presenting adverse events, stratified by type of event and grade. Adverse Events of special interest: Only relevant differences in toxicity by arm.
measure: Progresion Free Survival Median Values
time frame: Through the whole study. 4 years. The median follow up for each patient was 33.4 months
description: It will be measured following Response assessment in neuro-oncology (RANO) guidelines: progression-free survival
measure: Overall Survival
time frame: Through the whole study. 4 years. The median follow up for each patient was 33.4 months
description: Time between start of treatment and death
measure: Median Progression-free Survival (PFS) by Arm and MGMT Methylation Status
time frame: Through the whole study. 4 years. The median follow up for each patient was 33.4 months
description: Median Progression Free Survival depending on treatment arm in patients with MGMT methylation
measure: Median Overall Survival (OS) by Arm and MGMT Methylation Status
time frame: Through the whole study. 4 years. The median follow up for each patient was 33.4 months
description: Median OS depending on treatment arm in patients with methylated MGMT
measure: Translational Sub-study - Biomarkers: mutS Homolog 6 (MSH6) Immunoreactivity
time frame: baseline
description: partial immunoreactivity of MSH6 in patients by treatment arm. Tumor samples were stained by immuno-histochemical techniques.
arm group label: Temozolomide
arm group type: Experimental
description: Those patients will take 6 additional Temozolomide cycles
arm group label: Without treatment
arm group type: No Intervention
intervention type: Drug
intervention name: Temozolomide
arm group label: Temozolomide
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Carmen Balañá, M.D.
role: Study Chair
affiliation: Hospital Germans Trias i Pujol - ICO Badalona
last name: Mª Ángeles Vaz, M.D.
role: Study Chair
affiliation: Hospital Universitario Ramon y Cajal
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country: Spain
responsible party type: Sponsor
mesh term: Glioblastoma
mesh term: Temozolomide
provided document: 
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participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Our trial was not powered to detect significant differences in PFS or OS. To do so, we would have had to know the survival distribution for patients who complete the standard six cycles without progression, but this information was not available
point of contact: 