<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/NCT02970448</url>
  </required_header>
  <id_info>
    <org_study_id>CASE4316</org_study_id>
    <nct_id>NCT02970448</nct_id>
  </id_info>
  <brief_title>Expedited Laser Interstitial Thermal Therapy + Chemoradiation For Newly Diagnosed High Grade Gliomas</brief_title>
  <official_title>Expedited Laser Interstitial Thermal Therapy and Chemoradiation for Patients With Newly Diagnosed High Grade Gliomas</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Case Comprehensive Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Case Comprehensive Cancer Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators of this study want to see if shortening the total treatment time for brain&#xD;
      tumors is safe.The treatment for participant's brain tumors is laser surgery (Laser&#xD;
      Interstitial Thermal Therapy (LITT)) followed by radiation with chemotherapy. For&#xD;
      participants, the total time of treatment from surgery to the end of radiation and&#xD;
      chemotherapy is about l 0 weeks long. This study asks whether it is safe to shorten the total&#xD;
      treatment to 7 weeks.&#xD;
&#xD;
      To shorten the total treatment time, investigators want to see if it is safe to start&#xD;
      radiation with chemotherapy within 5 days after surgery. Usually patients start their&#xD;
      radiation with chemotherapy about 21-28 days after the surgery.&#xD;
&#xD;
      Shortening the total time of treatment may allow investigators to kill the cancer cells more&#xD;
      effectively.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Primary Objective To determine the safety and feasibility of reducing the time interval&#xD;
      between LITT and the start of chemoradiation to ≤ 7 days.&#xD;
&#xD;
      The primary endpoint (binary) for safety/feasibility will be defined as the occurrence of one&#xD;
      or more of the following within each patient during a window of observation from the&#xD;
      completion LITT to the end of radiation:&#xD;
&#xD;
        -  Wound dehiscence, grade 3 {CTCAE v4.0)&#xD;
&#xD;
        -  Seizures, grade 3 (CTCAE v4.0) in patients without a prior history of seizures and on&#xD;
           adequate anti-seizure medications&#xD;
&#xD;
        -  Cerebral edema, grade 4 (CTCAE v4.0)&#xD;
&#xD;
        -  Failure to complete of 60 Grays (Gy) of radiation&#xD;
&#xD;
      Secondary Objective(s) To estimate the proportion of patients requiring adjustments in&#xD;
      radiation plans post-LITT.&#xD;
&#xD;
      Secondary Endpoint: Requirement of an adjustment in the radiation plan to account for&#xD;
      post-LITT tissue distortion.&#xD;
&#xD;
      Study design This study will be a 2-stage, single-institution safety and feasibility trial.&#xD;
      Patients will be evaluated by a neuro-oncology team consisting of a neurosurgeon trained in&#xD;
      LITT, radiation oncologist and medical oncologist prior to surgery. Evaluable patients will&#xD;
      have a histologic diagnosis of high-grade glioma, complete LITT, and are candidates for&#xD;
      standard concurrent radiation (60 Gy) and temozolomide as determined by the treating&#xD;
      physician. Concurrent chemoradiation will begin within 7 days of the LITT procedure.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 24, 2017</start_date>
  <completion_date type="Anticipated">January 1, 2024</completion_date>
  <primary_completion_date type="Anticipated">January 1, 2024</primary_completion_date>
  <phase>Early 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>Study safety as determined by the number of patients who experience pre-specified adverse events</measure>
    <time_frame>Up to 12 weeks after LITT therapy</time_frame>
    <description>pre-specified adverse events include: Wound dehiscence, grade 3 (CTCAE v4.0), Grade 3 Seizures (CTCAE v4.0) in patients without a prior history of seizures and on adequate anti-seizure medications, Cerebral edema, grade 4 (CTCAE v4.0), Failure to complete of 60 Gy radiation</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of patients with adjustments to radiation plan to account for post-LITT tissue distortion</measure>
    <time_frame>Up to 12 weeks after LITT therapy</time_frame>
    <description>The proportion of patients requiring a change in radiation plan after fusion of the plan with the post-operative MRI will be calculated, and a 95% confidence interval will be placed on this proportion.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">45</enrollment>
  <condition>High Grade Glioma</condition>
  <arm_group>
    <arm_group_label>LITT with Radiation and Temozolomide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Laser interstitial thermal therapy (LITT) followed by Radiation therapy, three-dimensional conformal radiotherapy (3D-CRT) or intensity modulation radiation therapy (IMRT), 60 Gy/30 fractions. Radiation given with chemotherapy Temozolomide</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>LITT</intervention_name>
    <description>MRI-guided laser interstitial thermal therapy uses a gas cooled side-firing (directional) laser and a variety of procedure specific tools to thermally ablate target tissue in-situ.</description>
    <arm_group_label>LITT with Radiation and Temozolomide</arm_group_label>
    <other_name>Laser interstitial thermal therapy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Radiation therapy</intervention_name>
    <description>One treatment of 2 Gy will be given daily 5 days per week for a total of 60 Gy over 6 weeks. All portals shall be treated during each treatment session. Doses are specified such that at least 95% of the planning target volume (PTV) shall receive 100% of the prescribed dose.</description>
    <arm_group_label>LITT with Radiation and Temozolomide</arm_group_label>
    <other_name>3D-Conformal radiation therapy (RT)</other_name>
    <other_name>Intensity Modulated RT</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Temozolomide</intervention_name>
    <description>Temozolomide will be administered continuously from day 1 of radiotherapy to the last day of radiation at a daily oral dose of 75 mg/m2 for a maximum of 49 days</description>
    <arm_group_label>LITT with Radiation and Temozolomide</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects must have suspected high grade glioma by MRI&#xD;
&#xD;
          -  Subjects must have received no prior therapies for this disease.&#xD;
&#xD;
          -  Patients must be considered appropriate candidates for LITT.&#xD;
&#xD;
          -  Karnofsky Performance status ≥ 60%&#xD;
&#xD;
          -  Subjects must have normal organ and marrow function as defined below. Measures of&#xD;
             function must be within 14 days prior to registration.&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) ≥ 1500 cells/mm3, platelets ≥ 100,000 cells/mm3,&#xD;
                  hemoglobin ≥ 10.0 g/dl. Use of transfusion or other intervention to achieve this&#xD;
                  hemoglobin level is acceptable.&#xD;
&#xD;
               -  Blood urea nitrogen ≤ 30mg/dl and creatinine ≤ 1.7 mg/dl&#xD;
&#xD;
               -  Bilirubin ≤ 2.0 mg/dl, Aspartate aminotransferase/ Alanine aminotransferase&#xD;
                  (AST/ALT) ≤ 3x upper limit of normal&#xD;
&#xD;
               -  Electrocardiogram without evidence of acute cardiac ischemia&#xD;
&#xD;
               -  Prothrombin time/international normalized ratio (PT INR) &lt;1.4&#xD;
&#xD;
          -  Women of childbearing potential and male participants must practice adequate&#xD;
             contraception.&#xD;
&#xD;
          -  For women of childbearing age, negative pregnancy test within 14 days prior to&#xD;
             registration&#xD;
&#xD;
          -  Subjects must have the ability to understand and the willingness to sign a written&#xD;
             informed consent document.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participants not eligible to obtain MRI with and without contrast&#xD;
&#xD;
          -  Recurrent High grade gliomas (HGG)&#xD;
&#xD;
          -  Cerebral edema, grade 3 or greater prior to surgery&#xD;
&#xD;
          -  Post-operative complications including significant neurological decline or hemorrhage&#xD;
             that causes a drop in KPS to less than 60 or renders the patient not suitable for&#xD;
             chemoradiation as determined by their treating physician&#xD;
&#xD;
          -  Severe co-morbidity that would confer excess risk of surgery, radiation or&#xD;
             chemotherapy, as determined by the treating physician.&#xD;
&#xD;
        Any other major medical illnesses or psychiatric impairments that in the investigator's&#xD;
        opinion will prevent administration of completion of protocol therapy&#xD;
&#xD;
          -  Any other major medical illnesses or psychiatric impairments that in the&#xD;
             investigator's opinion will prevent administration or completion of protocol therapy.&#xD;
&#xD;
          -  Pregnancy or women of childbearing potential and men who are sexually active and not&#xD;
             willing/able to use medically acceptable forms of contraception; this exclusion is&#xD;
             necessary because the treatment involved in this study may be significantly&#xD;
             teratogenic.&#xD;
&#xD;
          -  Participants receiving other investigational agents.&#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>Jennifer Yu, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jennifer Yu, MD, PhD</last_name>
    <phone>1-866-223-8100</phone>
    <email>TaussigResearch@ccf.org</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Teresa Allison</last_name>
    <phone>1-866-223-8100</phone>
    <email>TaussigResearch@ccf.org</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jennifer Yu, MD, PhD</last_name>
      <phone>866-223-8100</phone>
      <email>TaussigResearch@ccf.org</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>November 18, 2016</study_first_submitted>
  <study_first_submitted_qc>November 21, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 22, 2016</study_first_posted>
  <last_update_submitted>July 24, 2023</last_update_submitted>
  <last_update_submitted_qc>July 24, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 25, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>LITT</keyword>
  <keyword>Brain Tumor</keyword>
  <keyword>Temozolomide</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glioma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Temozolomide</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02970448
org study id: CASE4316
nct id: NCT02970448
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
The investigators of this study want to see if shortening the total treatment time for brain
      tumors is safe.The treatment for participant's brain tumors is laser surgery (Laser
      Interstitial Thermal Therapy (LITT)) followed by radiation with chemotherapy. For
      participants, the total time of treatment from surgery to the end of radiation and
      chemotherapy is about l 0 weeks long. This study asks whether it is safe to shorten the total
      treatment to 7 weeks.

      To shorten the total treatment time, investigators want to see if it is safe to start
      radiation with chemotherapy within 5 days after surgery. Usually patients start their
      radiation with chemotherapy about 21-28 days after the surgery.

      Shortening the total time of treatment may allow investigators to kill the cancer cells more
      effectively.
Primary Objective To determine the safety and feasibility of reducing the time interval
      between LITT and the start of chemoradiation to ≤ 7 days.

      The primary endpoint (binary) for safety/feasibility will be defined as the occurrence of one
      or more of the following within each patient during a window of observation from the
      completion LITT to the end of radiation:

        -  Wound dehiscence, grade 3 {CTCAE v4.0)

        -  Seizures, grade 3 (CTCAE v4.0) in patients without a prior history of seizures and on
           adequate anti-seizure medications

        -  Cerebral edema, grade 4 (CTCAE v4.0)

        -  Failure to complete of 60 Grays (Gy) of radiation

      Secondary Objective(s) To estimate the proportion of patients requiring adjustments in
      radiation plans post-LITT.

      Secondary Endpoint: Requirement of an adjustment in the radiation plan to account for
      post-LITT tissue distortion.

      Study design This study will be a 2-stage, single-institution safety and feasibility trial.
      Patients will be evaluated by a neuro-oncology team consisting of a neurosurgeon trained in
      LITT, radiation oncologist and medical oncologist prior to surgery. Evaluable patients will
      have a histologic diagnosis of high-grade glioma, complete LITT, and are candidates for
      standard concurrent radiation (60 Gy) and temozolomide as determined by the treating
      physician. Concurrent chemoradiation will begin within 7 days of the LITT procedure.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Study safety as determined by the number of patients who experience pre-specified adverse events
time frame: Up to 12 weeks after LITT therapy
description: pre-specified adverse events include: Wound dehiscence, grade 3 (CTCAE v4.0), Grade 3 Seizures (CTCAE v4.0) in patients without a prior history of seizures and on adequate anti-seizure medications, Cerebral edema, grade 4 (CTCAE v4.0), Failure to complete of 60 Gy radiation
measure: Number of patients with adjustments to radiation plan to account for post-LITT tissue distortion
time frame: Up to 12 weeks after LITT therapy
description: The proportion of patients requiring a change in radiation plan after fusion of the plan with the post-operative MRI will be calculated, and a 95% confidence interval will be placed on this proportion.
arm group label: LITT with Radiation and Temozolomide
arm group type: Experimental
description: Laser interstitial thermal therapy (LITT) followed by Radiation therapy, three-dimensional conformal radiotherapy (3D-CRT) or intensity modulation radiation therapy (IMRT), 60 Gy/30 fractions. Radiation given with chemotherapy Temozolomide
intervention type: Procedure
intervention name: LITT
description: MRI-guided laser interstitial thermal therapy uses a gas cooled side-firing (directional) laser and a variety of procedure specific tools to thermally ablate target tissue in-situ.
arm group label: LITT with Radiation and Temozolomide
other name: Laser interstitial thermal therapy
intervention type: Radiation
intervention name: Radiation therapy
description: One treatment of 2 Gy will be given daily 5 days per week for a total of 60 Gy over 6 weeks. All portals shall be treated during each treatment session. Doses are specified such that at least 95% of the planning target volume (PTV) shall receive 100% of the prescribed dose.
arm group label: LITT with Radiation and Temozolomide
other name: 3D-Conformal radiation therapy (RT)
other name: Intensity Modulated RT
intervention type: Drug
intervention name: Temozolomide
description: Temozolomide will be administered continuously from day 1 of radiotherapy to the last day of radiation at a daily oral dose of 75 mg/m2 for a maximum of 49 days
arm group label: LITT with Radiation and Temozolomide
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jennifer Yu, MD, PhD
role: Principal Investigator
affiliation: Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center
last name: Jennifer Yu, MD, PhD
phone: 1-866-223-8100
email: TaussigResearch@ccf.org
last name: Teresa Allison
phone: 1-866-223-8100
email: TaussigResearch@ccf.org
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Sponsor
mesh term: Glioma
mesh term: Temozolomide