<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/NCT01668082</url>
  </required_header>
  <id_info>
    <org_study_id>STU 062010-157</org_study_id>
    <nct_id>NCT01668082</nct_id>
  </id_info>
  <brief_title>An Investigation of Brain Tumor Metabolism in Patients Undergoing Surgical Resection</brief_title>
  <official_title>An Investigation of Brain Tumor Metabolism in Patients Undergoing Surgical Resection</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Texas Southwestern Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Texas Southwestern Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study is designed to use infusion of a non-radioactive, naturally occurring isotope of&#xD;
      glucose (13C) in patients undergoing surgical resection for a newly identified brain mass to&#xD;
      obtain the metabolic phenotype of the tumor, and correlate it with the histopathological&#xD;
      diagnosis. In each patient, 13C NMR spectral analysis of tumor extracts will be obtained&#xD;
      after intraoperative infusion of [U-13C]glucose or [1,2-13C]glucose. Whenever feasible,&#xD;
      patients will undergo 3 preoperative imaging studies - 18FDG-PET, diffusion tensor imaging&#xD;
      with 1H-spectroscopy on 3T MR scanner, and ultra high resolution MR imaging on the 7T MR&#xD;
      scanner. The results of these imaging studies will be correlated with the metabolic phenotype&#xD;
      to generate a comprehensive non-invasive view of the tumor with the goal of identifying&#xD;
      infiltrative, metabolically active tumor cells within the brain. In addition, a comprehensive&#xD;
      molecular profile of the tumor will be obtained and enable a genotype-metabolic phenotype&#xD;
      comparative analysis.&#xD;
&#xD;
      Correlative Translational Research The investigators will obtain tumor tissue from each&#xD;
      patient for comprehensive molecular analysis (array CGH, expression profiling, methylation&#xD;
      profiling) which will be correlated with tumor histology, the metabolites identified by 1H-MR&#xD;
      spectroscopy and the 13Cglucose metabolic profile. Patients will be followed at designated&#xD;
      time points along their treatment course to obtain information about ongoing treatment and&#xD;
      response, time to tumor progression and overall survival. These parameters will be used in&#xD;
      correlational analysis with the metabolic phenotype.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study is designed to obtain tumor samples from patients undergoing clinically indicated&#xD;
      surgical resection of a brain tumor or primary non-CNS tumor after infusion of 13C-glucose,&#xD;
      13C-acetate or 13C-glucose and 13C-acetate. Patients with a brain mass identified on brain&#xD;
      imaging and who need surgical resection of the mass will be eligible for this metabolism&#xD;
      study. Eligible study patients will be screened, recruited, and enrolled at UT Southwestern&#xD;
      Medical Center in the Harold C. Simmons Comprehensive Cancer Center, University Hospital -&#xD;
      Zale Lipshy and University Hospital - St. Paul, Children's Medical Center of Dallas as well&#xD;
      as at Parkland Health and Hospital System. We will consent 60 patients, including projected&#xD;
      screen failures and early withdrawals, and anticipate that we will study 25 patients in this&#xD;
      clinical protocol. Once enrolled, patients will undergo a series of preoperative brain&#xD;
      imaging studies including 3T MRI with Diffusion Tensor Imaging (DTI) and 1H-MR spectroscopy,&#xD;
      7T MRI and a brain 18FDG-PET scan within 7-14 days of the scheduled operation. Of these&#xD;
      studies, only the 3T MRI is standard of care. The DTI and 1H-MR spectroscopy are additional&#xD;
      scanning sequences that are being done for research purposes. Similarly, the 7T MRI and the&#xD;
      18FDG-PET are being done for research purposes only. On the day of surgery, the patient will&#xD;
      have a peripheral IV started while waiting in the preoperative holding area and a 20%&#xD;
      solution of either [U-13C]glucose and/or [1,2-13C]acetate (to be determined for each&#xD;
      individual patient by the PI) will be infused at a rate of 4g/hr for a maximum of 4 hours.&#xD;
      During the infusion period, 4 timed blood samples will be collected for NMR analysis of&#xD;
      13C-glucose in the blood. The infusion will continue until the tumor has been resected and&#xD;
      samples have been collected and flash frozen for 13C-NMR spectral analysis and molecular&#xD;
      analyses. The infusion and tumor collection for 13C-NMR analysis is being done for research&#xD;
      purposes only. However, the remainder of the neurosurgical operative and post-operative&#xD;
      procedures will be followed according to standard practice. The patient will be seen 10-14&#xD;
      days after surgery for a follow up visit at which time an assessment of adverse events will&#xD;
      be performed. Thereafter, every 6 months for 5 years or until death, the patient will be&#xD;
      contacted and data regarding treatment, responses, and tumor progression will be collected&#xD;
      for correlative analysis.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 2009</start_date>
  <completion_date type="Anticipated">February 2025</completion_date>
  <primary_completion_date type="Anticipated">February 2024</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>metabolic phenotype correlation to clinical endpoints</measure>
    <time_frame>at end of follow-up period- between days 1-14</time_frame>
    <description>To correlate the metabolic phenotype obtained from histopathological diagnosis with the clinical endpoints of time to tumor progression and overall survival during the 5 years of patient follow-up</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>baseline imaging data review</measure>
    <time_frame>at time of study entry- within 14 days of surgery</time_frame>
    <description>To compare and contrast baseline imaging data obtained on the 7T MR among the major brain tumor histological subtypes (e.g. low grade gliomas, glioblastoma, brain metastases) with emphasis on the differences in vascular integrity and extent of tumor infiltration for each subtype</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>molecular profiling</measure>
    <time_frame>after surgical resection- day 0</time_frame>
    <description>To correlate changes on 7T with the molecular profile of the primary resected tumor (molecular profiling is being done under a separate IRB approved protocol).</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Brain Mass</condition>
  <arm_group>
    <arm_group_label>surgical resection of a brain tumor</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The patient will undergo surgical removal of the tumor after infusion of 13C-glucose using standard neurosurgical technique, including frameless stereotaxy for surgical navigation, and microsurgical technique.&#xD;
--------------------------------------------------------------------------------</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>surgical resection of a brain tumor</intervention_name>
    <description>The patient will undergo surgical removal of the tumor after infusion of 13C-glucose using standard neurosurgical technique, including frameless stereotaxy for surgical navigation, and microsurgical technique.</description>
    <arm_group_label>surgical resection of a brain tumor</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female, any age and any racial or ethnic group&#xD;
&#xD;
          -  Spanish-speaking patients will be eligible&#xD;
&#xD;
          -  Pre-operative brain MR imaging suggestive of a brain tumor or pre-operative imaging&#xD;
             showing a tumor or biopsy of a tumor mass prior to planned resection of the mass&#xD;
&#xD;
          -  Patient able and willing to provide informed consent or Legal parent or guardian&#xD;
             willing and able to provide informed consent for patient under age 18.&#xD;
&#xD;
          -  Karnofsky Performance status &gt; 70%&#xD;
&#xD;
          -  Negative serum pregnancy test or child bearing potential terminated by surgery,&#xD;
             radiation, menopause or current use of two approved methods of birth control&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient or legal parent/guardian unable to provide informed consent&#xD;
&#xD;
          -  Karnofsky Performance status &lt; 70%&#xD;
&#xD;
          -  Patients who are claustrophobic or have other contraindications to MRI, such as&#xD;
             impanted pacemaker device vascular clips, surgical clips, prosthetic valves,&#xD;
             pacemakers, otologic implants&#xD;
&#xD;
          -  NYHA class III and IV congestive heart failure&#xD;
&#xD;
          -  Psychiatric or addictive disorders that preclude obtaining informed consent&#xD;
&#xD;
          -  Unstable angina&#xD;
&#xD;
          -  Pregnant or lactating women&#xD;
&#xD;
          -  Women of childbearing potential who refuse a pregnancy test (performed during&#xD;
             screening)&#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>Elizabeth Maher, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Texas</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Elizabeth Maher, MD, PhD</last_name>
    <phone>214-648-7097</phone>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Omar Raslan, MBBCH,MPH, CCRP</last_name>
    <phone>214-648-7097</phone>
    <email>omar.raslan@utsouthwestern.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University of Texas Southwestern</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Elizabeth Maher, MD, PhD</last_name>
      <phone>214-648-7097</phone>
      <email>elizabeth.maher@utsouthwestern.edu</email>
    </contact>
    <investigator>
      <last_name>Craig Malloy, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Changho Choi, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Bruce Mickey, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Christopher Madden, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Robert Bachoo, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Ralph Deberardinis, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Juan Pascual, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Kimmo Hatanpaa, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Jack Raisanen, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Daniel Bowers, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Laura Klesse, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Bradley Weprin, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Kevin Courtney, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Patrick Leavey, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>June 12, 2012</study_first_submitted>
  <study_first_submitted_qc>August 15, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 17, 2012</study_first_posted>
  <last_update_submitted>April 20, 2023</last_update_submitted>
  <last_update_submitted_qc>April 20, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 24, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Texas Southwestern Medical Center</investigator_affiliation>
    <investigator_full_name>Elizabeth Maher</investigator_full_name>
    <investigator_title>Professor of Medicine</investigator_title>
  </responsible_party>
  <keyword>Patients with newly identified brain mass</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brain Neoplasms</mesh_term>
  </condition_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/NCT01668082
org study id: STU 062010-157
nct id: NCT01668082
lead sponsor: 
has dmc: Yes
The study is designed to use infusion of a non-radioactive, naturally occurring isotope of
      glucose (13C) in patients undergoing surgical resection for a newly identified brain mass to
      obtain the metabolic phenotype of the tumor, and correlate it with the histopathological
      diagnosis. In each patient, 13C NMR spectral analysis of tumor extracts will be obtained
      after intraoperative infusion of [U-13C]glucose or [1,2-13C]glucose. Whenever feasible,
      patients will undergo 3 preoperative imaging studies - 18FDG-PET, diffusion tensor imaging
      with 1H-spectroscopy on 3T MR scanner, and ultra high resolution MR imaging on the 7T MR
      scanner. The results of these imaging studies will be correlated with the metabolic phenotype
      to generate a comprehensive non-invasive view of the tumor with the goal of identifying
      infiltrative, metabolically active tumor cells within the brain. In addition, a comprehensive
      molecular profile of the tumor will be obtained and enable a genotype-metabolic phenotype
      comparative analysis.

      Correlative Translational Research The investigators will obtain tumor tissue from each
      patient for comprehensive molecular analysis (array CGH, expression profiling, methylation
      profiling) which will be correlated with tumor histology, the metabolites identified by 1H-MR
      spectroscopy and the 13Cglucose metabolic profile. Patients will be followed at designated
      time points along their treatment course to obtain information about ongoing treatment and
      response, time to tumor progression and overall survival. These parameters will be used in
      correlational analysis with the metabolic phenotype.
The study is designed to obtain tumor samples from patients undergoing clinically indicated
      surgical resection of a brain tumor or primary non-CNS tumor after infusion of 13C-glucose,
      13C-acetate or 13C-glucose and 13C-acetate. Patients with a brain mass identified on brain
      imaging and who need surgical resection of the mass will be eligible for this metabolism
      study. Eligible study patients will be screened, recruited, and enrolled at UT Southwestern
      Medical Center in the Harold C. Simmons Comprehensive Cancer Center, University Hospital -
      Zale Lipshy and University Hospital - St. Paul, Children's Medical Center of Dallas as well
      as at Parkland Health and Hospital System. We will consent 60 patients, including projected
      screen failures and early withdrawals, and anticipate that we will study 25 patients in this
      clinical protocol. Once enrolled, patients will undergo a series of preoperative brain
      imaging studies including 3T MRI with Diffusion Tensor Imaging (DTI) and 1H-MR spectroscopy,
      7T MRI and a brain 18FDG-PET scan within 7-14 days of the scheduled operation. Of these
      studies, only the 3T MRI is standard of care. The DTI and 1H-MR spectroscopy are additional
      scanning sequences that are being done for research purposes. Similarly, the 7T MRI and the
      18FDG-PET are being done for research purposes only. On the day of surgery, the patient will
      have a peripheral IV started while waiting in the preoperative holding area and a 20%
      solution of either [U-13C]glucose and/or [1,2-13C]acetate (to be determined for each
      individual patient by the PI) will be infused at a rate of 4g/hr for a maximum of 4 hours.
      During the infusion period, 4 timed blood samples will be collected for NMR analysis of
      13C-glucose in the blood. The infusion will continue until the tumor has been resected and
      samples have been collected and flash frozen for 13C-NMR spectral analysis and molecular
      analyses. The infusion and tumor collection for 13C-NMR analysis is being done for research
      purposes only. However, the remainder of the neurosurgical operative and post-operative
      procedures will be followed according to standard practice. The patient will be seen 10-14
      days after surgery for a follow up visit at which time an assessment of adverse events will
      be performed. Thereafter, every 6 months for 5 years or until death, the patient will be
      contacted and data regarding treatment, responses, and tumor progression will be collected
      for correlative analysis.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: metabolic phenotype correlation to clinical endpoints
time frame: at end of follow-up period- between days 1-14
description: To correlate the metabolic phenotype obtained from histopathological diagnosis with the clinical endpoints of time to tumor progression and overall survival during the 5 years of patient follow-up
measure: baseline imaging data review
time frame: at time of study entry- within 14 days of surgery
description: To compare and contrast baseline imaging data obtained on the 7T MR among the major brain tumor histological subtypes (e.g. low grade gliomas, glioblastoma, brain metastases) with emphasis on the differences in vascular integrity and extent of tumor infiltration for each subtype
measure: molecular profiling
time frame: after surgical resection- day 0
description: To correlate changes on 7T with the molecular profile of the primary resected tumor (molecular profiling is being done under a separate IRB approved protocol).
arm group label: surgical resection of a brain tumor
arm group type: Experimental
description: The patient will undergo surgical removal of the tumor after infusion of 13C-glucose using standard neurosurgical technique, including frameless stereotaxy for surgical navigation, and microsurgical technique.
--------------------------------------------------------------------------------
intervention type: Procedure
intervention name: surgical resection of a brain tumor
description: The patient will undergo surgical removal of the tumor after infusion of 13C-glucose using standard neurosurgical technique, including frameless stereotaxy for surgical navigation, and microsurgical technique.
arm group label: surgical resection of a brain tumor
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Elizabeth Maher, MD, PhD
role: Principal Investigator
affiliation: University of Texas
last name: Elizabeth Maher, MD, PhD
phone: 214-648-7097
last name: Omar Raslan, MBBCH,MPH, CCRP
phone: 214-648-7097
email: omar.raslan@utsouthwestern.edu
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Texas Southwestern Medical Center
investigator full name: Elizabeth Maher
investigator title: Professor of Medicine
mesh term: Brain Neoplasms
sharing ipd: No