<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/NCT03243851</url>
  </required_header>
  <id_info>
    <org_study_id>KNOG-1501</org_study_id>
    <nct_id>NCT03243851</nct_id>
  </id_info>
  <brief_title>Study on Low Dose Temozolomide Plus Metformin or Placebo in Patient With Recurrent or Refractory Glioblastoma</brief_title>
  <acronym>METT</acronym>
  <official_title>Efficacy and Safety of Low Dose Temozolomide Plus Metformin as Combination Chemotherapy Compared With Low Dose Temozolomide Plus Placebo in Patient With Recurrent or Refractory Glioblastoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Yong-Kil Hong</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Saint Vincent's Hospital, Korea</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Incheon St.Mary's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Cancer Center, Korea</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Konkuk University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Seoul National University Bundang Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Samsung Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Seoul National University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Asan Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Ajou University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Severance Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Chonnam National University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Seoul St. Mary's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Seoul St. Mary's Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      A phase 2 clinical trial for the efficacy and safety of low dose Temozolomide plus metformin&#xD;
      as combination chemotherapy compared with low dose Temozolomide plus placebo in patient with&#xD;
      recurrent or refractory Glioblastoma&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Studies will investigate the efficacy and safety of low dose Temozolomide with Metformin or&#xD;
      placebo for the patients with recurrent or refractory Glioblastoma.&#xD;
&#xD;
      The dosage of the Metformin will follow the domestically permitted dose to minimize side&#xD;
      effects.&#xD;
&#xD;
      The patients will be allocated randomly to arm 1(experimental) and arm 2(placebo controlled)&#xD;
      and administered the investigational products for up to 6 cycle. Each cycle consists of 4&#xD;
      weeks.&#xD;
&#xD;
      After 6 cycle(24 weeks), the patients will be checked progression and survival every 24 weeks&#xD;
      up to 96 weeks.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 21, 2016</start_date>
  <completion_date type="Actual">December 31, 2020</completion_date>
  <primary_completion_date type="Actual">December 31, 2020</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>
    <intervention_model_description>Arm 1 : Low dose temozolomide+metformin Arm 2 : Low dose temozolomide+placebo</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Double blinded</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Comparison of progression-free survival obtained from progression-free survival curve</measure>
    <time_frame>24 weeks</time_frame>
    <description>Comparison of progression-free survival obtained from progression-free survival curve</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Response Rate</measure>
    <time_frame>4 weeks, 8 weeks, 16 weeks, 24 weeks thereafter every 24 weeks up to 96 weeks</time_frame>
    <description>Tumor Response Rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tumor control probability</measure>
    <time_frame>4 weeks, 8 weeks, 16 weeks, 24 weeks thereafter every 24 weeks up to 96 weeks</time_frame>
    <description>Tumor control probability</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>6 month progression free survival</measure>
    <time_frame>24 weeks</time_frame>
    <description>6 month progression free survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>6 month overall survival</measure>
    <time_frame>24 weeks</time_frame>
    <description>6 month overall survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of the quality of life of cancer patients</measure>
    <time_frame>4 weeks, 8 weeks, 16 weeks, 24 weeks</time_frame>
    <description>EORTC QLQ-C30 and EORTC QLQ-BN20</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">81</enrollment>
  <condition>Glioblastoma</condition>
  <arm_group>
    <arm_group_label>Temozolomide+metformin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Temozolomide :&#xD;
1 cycle of 4 weeks with daily dose 50mg/m2(BSA: Body Surface Area) up to 6 cycles for 24 weeks&#xD;
Metformin :&#xD;
1st cycle (4 weeks)&#xD;
1 week(1st~7th day) = 1,000mg/day&#xD;
1 week(8th~14th day) = 1,500mg/day&#xD;
2 weeks(15th ~28th day) = 2,000mg/day&#xD;
2nd to 6th cycle (20 weeks) = 2,000mg/day</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Temozolomide+placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Temozolomide :&#xD;
1 cycle of 4 weeks with daily dose 50mg/m2(BSA: Body Surface Area) up to 6 cycles for 24 weeks&#xD;
Placebo:&#xD;
1st cycle (4 weeks)&#xD;
1 week(1st~7th day) = 1,000mg/day&#xD;
1 week(8th~14th day) = 1,500mg/day&#xD;
2 weeks(15th~28th day) = 2,000mg/day&#xD;
2nd to 6th cycle (20 weeks) = 2,000mg/day</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Temozolomide+Metformin</intervention_name>
    <description>Low dose temozolomide+metformin for 24 weeks</description>
    <arm_group_label>Temozolomide+metformin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Temozolomide+Placebo</intervention_name>
    <description>Low dose temozolomide+placebo for 24 weeks</description>
    <arm_group_label>Temozolomide+placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Progressive or recurrent Glioblastoma conformed by histopathological or radiological&#xD;
             diagnosis. Progressive or recurrent Glioblastoma during or after standard therapy&#xD;
             (Temozolomide after Temozolomide and radiation therapy; Stupp regimen) after&#xD;
             histopathological diagnosis of Glioblastoma Recurrence or progression is diagnosed&#xD;
             according to histopathological diagnosis or revised RANO(Response Assessment in&#xD;
             Neuro-Oncology) criteria c&#xD;
&#xD;
          2. Karnofsky performance status(KPS) ≥ 60%&#xD;
&#xD;
          3. Age ≥ 19 years old&#xD;
&#xD;
          4. At least 4 weeks after operation or chemotherapy&#xD;
&#xD;
          5. Normal in hematological finding, liver and kidney function&#xD;
&#xD;
               -  Hematology ANC &gt; 1.500/mm³, Platelet &gt; 100,000/mm³, WBC &gt; 3×10^9/L, Hemoglobin &gt;&#xD;
                  9g/dL&#xD;
&#xD;
               -  Liver function Total Bilirubin level ≤ 1.5×ULN(in case of isolated&#xD;
                  hyperbilirubinemia ≤2.5 x ULN) AST / ALT &lt; 2.5×ULN&#xD;
&#xD;
               -  Renal function Serum creatinine ≤ 1.5mg/dL&#xD;
&#xD;
          6. Be informed of the nature of the study and obtained a written informed consent&#xD;
&#xD;
          7. A legal representative agrees to the trial when a subject is unable to communicate&#xD;
             smoothly due to neurologic defect&#xD;
&#xD;
          8. If a fertile woman who has been confirmed negative to a urine or blood pregnancy test&#xD;
             within 28 days prior to the trial&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Pregnant or breast feeding&#xD;
&#xD;
          2. Cancer history within 5 years excluding cancer in the skin cells and cervix&#xD;
&#xD;
          3. Active infections within two weeks&#xD;
&#xD;
          4. Leptomeningeal metastasis&#xD;
&#xD;
          5. Patients diagnosed with diabetes&#xD;
&#xD;
          6. Hypersensitive or intolerance to Metformin&#xD;
&#xD;
          7. Patients who are currently taking Metformin, sulfonylureas, thiazolidinediones, and&#xD;
             insulin, regardless of reason&#xD;
&#xD;
          8. Other serious diseases or medical conditions that include :&#xD;
&#xD;
               -  Patients who suffer from unstable heart disease despite treatment.&#xD;
&#xD;
               -  Patients having a heart attack within 6 months prior to the start of trial&#xD;
&#xD;
               -  Patients who suffer from severe nerve or psychosis that includes dementia or&#xD;
                  strokes.&#xD;
&#xD;
               -  Patients with an uncontrolled infection&#xD;
&#xD;
               -  Patient with uncontrolled hypertension, congestive heart failure, unstable&#xD;
                  angina, or incomplete arrhythmia&#xD;
&#xD;
          9. Those who have participated in other clinical trials may not recover from the toxicity&#xD;
             of the treatment.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Yong-Kil Hong, MD.,PhD.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Seoul St. Mary's Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Cancer Center Korea</name>
      <address>
        <city>Ilsan</city>
        <state>Gyeonggi-Do</state>
        <zip>10408</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul National University Bundang Hospital</name>
      <address>
        <city>Seongnam-si</city>
        <state>Gyeonggi-Do</state>
        <zip>13620</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ajou University Hospital</name>
      <address>
        <city>Suwon-si</city>
        <state>Gyeonggi-Do</state>
        <zip>16499</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chonnam National University Hwasun Hospital</name>
      <address>
        <city>Hwasun</city>
        <state>Jeollanam-Do</state>
        <zip>58128</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Incheon St. Mary's Hospital</name>
      <address>
        <city>Incheon</city>
        <zip>21431</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul National University Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>03080</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Severance Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>03722</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Konkuk University Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>05030</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Asan Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>05505</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Samsung Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>06351</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul St Mary's Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>06591</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Vincent's Hospital, Korea</name>
      <address>
        <city>Suwon-si</city>
        <zip>16247</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>July 29, 2017</study_first_submitted>
  <study_first_submitted_qc>August 4, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 9, 2017</study_first_posted>
  <last_update_submitted>September 8, 2021</last_update_submitted>
  <last_update_submitted_qc>September 8, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 9, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Seoul St. Mary's Hospital</investigator_affiliation>
    <investigator_full_name>Yong-Kil Hong</investigator_full_name>
    <investigator_title>MD., PhD.</investigator_title>
  </responsible_party>
  <keyword>Glioblastoma</keyword>
  <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>Metformin</mesh_term>
    <mesh_term>Temozolomide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03243851
org study id: KNOG-1501
nct id: NCT03243851
lead sponsor: 
collaborator: 
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has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
A phase 2 clinical trial for the efficacy and safety of low dose Temozolomide plus metformin
      as combination chemotherapy compared with low dose Temozolomide plus placebo in patient with
      recurrent or refractory Glioblastoma
Studies will investigate the efficacy and safety of low dose Temozolomide with Metformin or
      placebo for the patients with recurrent or refractory Glioblastoma.

      The dosage of the Metformin will follow the domestically permitted dose to minimize side
      effects.

      The patients will be allocated randomly to arm 1(experimental) and arm 2(placebo controlled)
      and administered the investigational products for up to 6 cycle. Each cycle consists of 4
      weeks.

      After 6 cycle(24 weeks), the patients will be checked progression and survival every 24 weeks
      up to 96 weeks.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Arm 1 : Low dose temozolomide+metformin Arm 2 : Low dose temozolomide+placebo
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Double blinded
measure: Comparison of progression-free survival obtained from progression-free survival curve
time frame: 24 weeks
description: Comparison of progression-free survival obtained from progression-free survival curve
measure: Response Rate
time frame: 4 weeks, 8 weeks, 16 weeks, 24 weeks thereafter every 24 weeks up to 96 weeks
description: Tumor Response Rate
measure: Tumor control probability
time frame: 4 weeks, 8 weeks, 16 weeks, 24 weeks thereafter every 24 weeks up to 96 weeks
description: Tumor control probability
measure: 6 month progression free survival
time frame: 24 weeks
description: 6 month progression free survival
measure: 6 month overall survival
time frame: 24 weeks
description: 6 month overall survival
measure: Assessment of the quality of life of cancer patients
time frame: 4 weeks, 8 weeks, 16 weeks, 24 weeks
description: EORTC QLQ-C30 and EORTC QLQ-BN20
arm group label: Temozolomide+metformin
arm group type: Experimental
description: Temozolomide :
1 cycle of 4 weeks with daily dose 50mg/m2(BSA: Body Surface Area) up to 6 cycles for 24 weeks
Metformin :
1st cycle (4 weeks)
1 week(1st~7th day) = 1,000mg/day
1 week(8th~14th day) = 1,500mg/day
2 weeks(15th ~28th day) = 2,000mg/day
2nd to 6th cycle (20 weeks) = 2,000mg/day
arm group label: Temozolomide+placebo
arm group type: Placebo Comparator
description: Temozolomide :
1 cycle of 4 weeks with daily dose 50mg/m2(BSA: Body Surface Area) up to 6 cycles for 24 weeks
Placebo:
1st cycle (4 weeks)
1 week(1st~7th day) = 1,000mg/day
1 week(8th~14th day) = 1,500mg/day
2 weeks(15th~28th day) = 2,000mg/day
2nd to 6th cycle (20 weeks) = 2,000mg/day
intervention type: Drug
intervention name: Temozolomide+Metformin
description: Low dose temozolomide+metformin for 24 weeks
arm group label: Temozolomide+metformin
intervention type: Drug
intervention name: Temozolomide+Placebo
description: Low dose temozolomide+placebo for 24 weeks
arm group label: Temozolomide+placebo
criteria: 
gender: All
minimum age: 19 Years
maximum age: N/A
healthy volunteers: No
last name: Yong-Kil Hong, MD.,PhD.
role: Principal Investigator
affiliation: Seoul St. Mary's Hospital
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country: Korea, Republic of
responsible party type: Sponsor-Investigator
investigator affiliation: Seoul St. Mary's Hospital
investigator full name: Yong-Kil Hong
investigator title: MD., PhD.
mesh term: Glioblastoma
mesh term: Metformin
mesh term: Temozolomide
sharing ipd: Undecided