<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/NCT04474353</url>
  </required_header>
  <id_info>
    <org_study_id>IRB-53582</org_study_id>
    <secondary_id>BRN0043</secondary_id>
    <secondary_id>IRB-53582</secondary_id>
    <nct_id>NCT04474353</nct_id>
  </id_info>
  <brief_title>Study of Tumor Treating Fields With Hypofractionated Chemoradiotherapy in Newly Diagnosed Glioblastoma</brief_title>
  <official_title>A Phase 1 Study of Tumor Treating Fields With 5 Day Hypofractionated Stereotactic Radiosurgery and Concurrent and Maintenance Temozolomide in Newly Diagnosed Glioblastoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Stanford University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>NovoCure Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Stanford University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine the safety and efficacy of the combination therapy&#xD;
      of TTFields + SRS+ Temozolomide (TMZ) for newly diagnosed glioblastoma (GBM).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Primary Objective:&#xD;
&#xD;
      Determine the safety of Tumor Treating Fields (TTFields) started concurrently with 5 fraction&#xD;
      stereotactic radiosurgery (SRS) and temozolomide for newly diagnosed glioblastoma. secondary&#xD;
      objective: Efficacy for the combination of TTFields started concurrently with 5&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">May 21, 2021</start_date>
  <completion_date type="Anticipated">May 2024</completion_date>
  <primary_completion_date type="Anticipated">November 2023</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Dose-limiting Toxicity (DLTs)</measure>
    <time_frame>5 months</time_frame>
    <description>Dose limiting toxicities (DLTs) are defined as possibly, probably, or definitely related adverse events that are severe or medically significant, and needing topical &amp; systemic therapy; needing surgery intervention; needing hospitalization; needing treatment interruption; or life threatening. Late DLTs will be assessed as the number of DLTs that occur in the period from 31 days after the start of treatment through 5 months after the start of treatment. The outcome will be reported as a number without dispersion.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Acute dose limiting toxicity</measure>
    <time_frame>1 month</time_frame>
    <description>Dose limiting toxicities (DLTs) are defined as possibly, probably, or definitely related adverse events that are severe or medically significant, and needing topical &amp; systemic therapy; needing surgery intervention; needing hospitalization; needing treatment interruption; or life threatening. Acute DLTs will be assessed as the number of DLTs that occur in the period from the start of treatment through 30 days after the start of treatment. The outcome will be reported as a number without dispersion.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival (PFS) at 6 Months</measure>
    <time_frame>6 months</time_frame>
    <description>Progression-free survival is defined as the number of evaluable participants who, at 6 months from the date of surgical resection or biopsy (PFS6), are alive without disease progression, death, or other defined event (study withdrawal or loss to follow up). Disease progression is defined as ≥ 25% increase in product of perpendicular diameters of the lesion; any increase in MRI T2/FLAIR lesion area from previous MRI scan; MRI detection of a new lesion; decline in clinical status not attributable to causes other than the tumor. The outcome will be reported as the number without dispersion.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>30 months</time_frame>
    <description>Overall survival (OS) will be assessed as the number of evaluable participants who remain alive from the date of surgical resection or biopsy. The outcome will be reported as the number without dispersion.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">12</enrollment>
  <condition>Glioblastoma</condition>
  <condition>Newly Diagnosed Glioblastoma</condition>
  <arm_group>
    <arm_group_label>Novo-TTF</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Day 1: Subjects will wear the Optune (TTFields device) for ≥ 18 hours/day. They will take off the device when receiving stereotactic radiosurgery and brain MRI scans.&#xD;
Days 1 to 8: Subjects will take oral temozolomide 75 mg/m2/day Days 2 to 8: Subjects will receive stereotactic radiosurgery (total of 35 Gy) divided equally over 5 days&#xD;
• After the interventional treatment, subjects will receive standard of care adjuvant chemotherapy and routine surveillance brain MRI scans.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Optune</intervention_name>
    <description>Noninvasive, portable device which generates tumor treating fields (TTFields) manufactured by Novocure</description>
    <arm_group_label>Novo-TTF</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gadolinium</intervention_name>
    <description>Gadolinium contrast medium</description>
    <arm_group_label>Novo-TTF</arm_group_label>
    <other_name>Contrast agent</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Temozolomide</intervention_name>
    <description>Chemotherapy agent</description>
    <arm_group_label>Novo-TTF</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Stereotactic radiosurgery (SRS)</intervention_name>
    <description>Standard of Care: SRS (35 Gy in 5 fractions of 7 Gy), 5-day treatment from Day 2</description>
    <arm_group_label>Novo-TTF</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histopathologically proven newly diagnosed glioblastoma (GBM, WHO Grade IV) or&#xD;
             molecular GBM of lower grade that will be treated as per glioblastoma (defined as IDH&#xD;
             wild type, 1p19q not co deleted)&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  A maximum tumor target diameter of less than 5 cm on the post operative MRI used for&#xD;
             SRS planning (a 5 mm margin is added in the radiotherapy planning process, yielding a&#xD;
             maximum diameter of the planning target volume (PTV) of less than 6 cm). If the&#xD;
             maximum diameter is greater than 5 cm, the subject is still eligible if the PTV is&#xD;
             less than 113 cm3 which is the volume of a 6 cm diameter sphere.&#xD;
&#xD;
          -  Adequate organ function (obtained within 14 days prior to Day 0) as evidenced by:&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) ≥ 1.5 × 109/L without myeloid growth factor&#xD;
                  support for 7 days preceding the lab assessment&#xD;
&#xD;
               -  Hemoglobin (Hgb) ≥ 9 g/dL (90 g/L); &lt; 9 g/dL (&lt; 90 g/L) is acceptable if&#xD;
                  hemoglobin is corrected to ≥ 9 g/dL (90 g/L) as by growth factor or transfusion&#xD;
                  prior to Day 0&#xD;
&#xD;
               -  Platelet count ≥ 100 × 109/L without blood transfusions for 7 days preceding the&#xD;
                  lab assessment&#xD;
&#xD;
               -  Bilirubin ≤ 1.5 × upper limit of normal (ULN), except for subjects with&#xD;
                  documented history of Gilbert's disease&#xD;
&#xD;
               -  Alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤ 2.5 × ULN&#xD;
&#xD;
               -  Alkaline phosphatase (AP) ≤ 3 × ULN&#xD;
&#xD;
               -  Women of childbearing potential (WCBP): negative serum pregnancy test (this test&#xD;
                  is required of all women unless post menopausal, defined as 12 consecutive months&#xD;
                  since last regular menses or surgically sterile)&#xD;
&#xD;
          -  Ability to tolerate MRI&#xD;
&#xD;
          -  Karnofsky Performance Scale (KPS) ≥ 60&#xD;
&#xD;
          -  Ability to understand and the willingness to sign (personally or by a legal authorized&#xD;
             representative) the written IRB approved informed consent document.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous chemotherapy or radiotherapy for glioma&#xD;
&#xD;
          -  Concurrent use of experimental therapies&#xD;
&#xD;
          -  Known allergy to adhesive tapes or other skin adhesives used in medical care&#xD;
&#xD;
          -  Known underlying skin hypersensitivity or other condition of the scalp with potential&#xD;
             toxicity per pre treatment dermatology evaluation&#xD;
&#xD;
          -  Subjects with the following co morbid disease or incurrent illness:&#xD;
&#xD;
               -  Subjects with known cirrhosis diagnosed with Child Pugh Class A or higher liver&#xD;
                  disease.&#xD;
&#xD;
               -  Prior malignancy except for non melanoma skin cancer and carcinoma in situ (of&#xD;
                  the cervix or bladder), unless diagnosed and definitively treated more than 3&#xD;
                  years prior to first dose of investigational drug&#xD;
&#xD;
               -  Severe/uncontrolled inter current illness within the previous 28 days prior to&#xD;
                  first day of treatment&#xD;
&#xD;
               -  Subjects who have implantable devices that are contra indicated for use with&#xD;
                  TTFields&#xD;
&#xD;
               -  Any other significant co morbid conditions that in the opinion of the&#xD;
                  investigator would impair study participation or cooperation.&#xD;
&#xD;
          -  Subjects receiving the following medications at the time of combined TTFields and SRS:&#xD;
&#xD;
               -  Pharmacotherapy for tuberculosis or HIV as these medications are known to&#xD;
                  interact with temozolomide&#xD;
&#xD;
               -  Other chemotherapy, other investigational agents, or biologic agents for the&#xD;
                  treatment of cancer including antibodies (eg, bevacizumab, trastuzumab,&#xD;
                  pertuzumab), small molecules, or any investigational agent(s).&#xD;
&#xD;
          -  Pregnant or nursing females will be excluded from the study&#xD;
&#xD;
          -  History of inability to tolerate MRI&#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>Scott G Soltys</last_name>
    <role>Principal Investigator</role>
    <affiliation>Stanford Universiy</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Aniket Pratapneni</last_name>
    <phone>650-725-2839</phone>
    <email>apratap1@stanford.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Stanford University</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94304</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Aniket Pratapneni</last_name>
      <phone>650-725-2839</phone>
      <email>apratap1@stanford.edu</email>
    </contact>
    <investigator>
      <last_name>Scott G Soltys</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>July 13, 2020</study_first_submitted>
  <study_first_submitted_qc>July 15, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 16, 2020</study_first_posted>
  <last_update_submitted>August 4, 2023</last_update_submitted>
  <last_update_submitted_qc>August 4, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 7, 2023</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>
  <patient_data>
    <sharing_ipd>No</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/NCT04474353
org study id: IRB-53582
secondary id: BRN0043
secondary id: IRB-53582
nct id: NCT04474353
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: Yes
is us export: No
The purpose of this study is to determine the safety and efficacy of the combination therapy
      of TTFields + SRS+ Temozolomide (TMZ) for newly diagnosed glioblastoma (GBM).
Primary Objective:

      Determine the safety of Tumor Treating Fields (TTFields) started concurrently with 5 fraction
      stereotactic radiosurgery (SRS) and temozolomide for newly diagnosed glioblastoma. secondary
      objective: Efficacy for the combination of TTFields started concurrently with 5
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Dose-limiting Toxicity (DLTs)
time frame: 5 months
description: Dose limiting toxicities (DLTs) are defined as possibly, probably, or definitely related adverse events that are severe or medically significant, and needing topical & systemic therapy; needing surgery intervention; needing hospitalization; needing treatment interruption; or life threatening. Late DLTs will be assessed as the number of DLTs that occur in the period from 31 days after the start of treatment through 5 months after the start of treatment. The outcome will be reported as a number without dispersion.
measure: Acute dose limiting toxicity
time frame: 1 month
description: Dose limiting toxicities (DLTs) are defined as possibly, probably, or definitely related adverse events that are severe or medically significant, and needing topical & systemic therapy; needing surgery intervention; needing hospitalization; needing treatment interruption; or life threatening. Acute DLTs will be assessed as the number of DLTs that occur in the period from the start of treatment through 30 days after the start of treatment. The outcome will be reported as a number without dispersion.
measure: Progression-free Survival (PFS) at 6 Months
time frame: 6 months
description: Progression-free survival is defined as the number of evaluable participants who, at 6 months from the date of surgical resection or biopsy (PFS6), are alive without disease progression, death, or other defined event (study withdrawal or loss to follow up). Disease progression is defined as ≥ 25% increase in product of perpendicular diameters of the lesion; any increase in MRI T2/FLAIR lesion area from previous MRI scan; MRI detection of a new lesion; decline in clinical status not attributable to causes other than the tumor. The outcome will be reported as the number without dispersion.
measure: Overall Survival (OS)
time frame: 30 months
description: Overall survival (OS) will be assessed as the number of evaluable participants who remain alive from the date of surgical resection or biopsy. The outcome will be reported as the number without dispersion.
arm group label: Novo-TTF
arm group type: Experimental
description: Day 1: Subjects will wear the Optune (TTFields device) for ≥ 18 hours/day. They will take off the device when receiving stereotactic radiosurgery and brain MRI scans.
Days 1 to 8: Subjects will take oral temozolomide 75 mg/m2/day Days 2 to 8: Subjects will receive stereotactic radiosurgery (total of 35 Gy) divided equally over 5 days
• After the interventional treatment, subjects will receive standard of care adjuvant chemotherapy and routine surveillance brain MRI scans.
intervention type: Device
intervention name: Optune
description: Noninvasive, portable device which generates tumor treating fields (TTFields) manufactured by Novocure
arm group label: Novo-TTF
intervention type: Drug
intervention name: Gadolinium
description: Gadolinium contrast medium
arm group label: Novo-TTF
other name: Contrast agent
intervention type: Drug
intervention name: Temozolomide
description: Chemotherapy agent
arm group label: Novo-TTF
intervention type: Radiation
intervention name: Stereotactic radiosurgery (SRS)
description: Standard of Care: SRS (35 Gy in 5 fractions of 7 Gy), 5-day treatment from Day 2
arm group label: Novo-TTF
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Scott G Soltys
role: Principal Investigator
affiliation: Stanford Universiy
last name: Aniket Pratapneni
phone: 650-725-2839
email: apratap1@stanford.edu
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Glioblastoma
mesh term: Temozolomide
sharing ipd: No