<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/NCT03262636</url>
  </required_header>
  <id_info>
    <org_study_id>0822231</org_study_id>
    <nct_id>NCT03262636</nct_id>
  </id_info>
  <brief_title>Two-Part Study to Evaluate the Safety and Efficacy of Image Guided Surgery Using Indocyanine Green for Intramolecular Imaging of Nervous System Tumors Compared to Standard of Care, (TumorGlow)</brief_title>
  <acronym>TumorGlow(TM)</acronym>
  <official_title>Two-Part Study to Evaluate the Safety and Efficacy of Image Guided Surgery Using Indocyanine Green for Intramolecular Imaging of Nervous System Tumors Compared to Standard of Care, (TumorGlow)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Pennsylvania</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Pennsylvania</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Primary malignant and non-malignant brain tumors account for an estimated 21.42 cases per&#xD;
      100,000 for a total count of 343,175 incident tumors based on worldwide population estimates&#xD;
      [1]. These entities result in variable but disappointing rates of survival, particularly for&#xD;
      primary brain tumors (5-year survival rates: anaplastic astrocytoma 27%; glioblastoma&#xD;
      multiforme 5%) [2, 3]. Metastatic brain tumors outnumber primary brain tumors (estimates as&#xD;
      high as 10:1) as they affect approximately 25% of patients diagnosed with cancer [4-6]. In&#xD;
      terms of brain tumor surgery, the extent of surgical resection-a factor that is greatly&#xD;
      impacted by a Neurosurgeon's ability to visualize these tumors-is directly associated with&#xD;
      patient outcomes and survival [7-9]. Although spinal cord tumors are lower in terms of their&#xD;
      incidence [10], data correlating extent-of-resection to outcomes and survival have been&#xD;
      demonstrated in patients with intramedullary tumors [11].&#xD;
&#xD;
      Using systemically delivered compounds with a high sensitivity of detection by near-infrared&#xD;
      (NIR) fluorescence, it would be possible for us to improve surgical resection thus minimizing&#xD;
      chances of recurrence and improving survival. Simply, if the tumor cells will &quot;glow&quot; during&#xD;
      surgery, the surgeons are more likely to identify tumor margins and residual disease, and&#xD;
      are, therefore more likely to perform a superior cancer operation. By ensuring a negative&#xD;
      margin through NIR imagery, it would make it possible to decrease the rates of recurrence and&#xD;
      thus improve overall survival.&#xD;
&#xD;
      This concept of intraoperative molecular imaging requires two innovations:&#xD;
&#xD;
      (i) a fluorescent contrast agent that can be injected systemically into the subject and that&#xD;
      selectively accumulates in the tumor tissues, and (ii) an imaging system that can detect and&#xD;
      quantify the contrast agent in the tumor tissues.[12, 13]&#xD;
&#xD;
      Subjects undergo intraoperative imaging, receiving an injection of indocyanine green and then&#xD;
      undergoing intraoperative imaging of the surgery site with a NIR imaging system. The imaging&#xD;
      devices allow the operating field to be observed in real-time.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Indocyanine green is a water-soluble tricarbocyanine dye routinely used in clinical settings&#xD;
      for measuring cardiac output, hepatic function, liver blood flow and ophthalmic angiography&#xD;
      and has been in use for over 60 years [14]. This protocol utilizes Patheon's indocyanine&#xD;
      green, NDC 17238-424. The chemical formula is C45H47N2O6S2Na and the compound has a molecular&#xD;
      weight of 774.96Da (CAS number 3599-32-4). It has a peak absorption in the NIR spectrum at&#xD;
      800nm and maximal emission at 835nm. Indocyanine green is rapidly and completely bound to&#xD;
      plasma proteins (especially albumin) after intravenous (IV) injection in the blood [15].&#xD;
&#xD;
      Indocyanine Green for Injection USP is a sterile, lyophilized green powder containing 25 mg&#xD;
      of indocyanine green with no more than 5% sodium iodide. It is packaged with Sterile Water&#xD;
      for Injection, USP, which is used to dissolve the indocyanine green, and is to be&#xD;
      administered intravenously&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>June 2015</start_date>
  <completion_date type="Actual">March 10, 2020</completion_date>
  <primary_completion_date type="Actual">March 10, 2020</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Determining the sensitivity of ICG uptake and expression in identifying ANS tumor deposits when excited by an imaging probe.</measure>
    <time_frame>36 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>optimize timing and dose of second window Indocyanine Green during surgery of nervous system tumors, based on sensitivity/specificity.</measure>
    <time_frame>36 months</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">363</enrollment>
  <condition>Brain Tumor, Primary</condition>
  <condition>Brain Tumor, Recurrent</condition>
  <arm_group>
    <arm_group_label>Diagnostic value of Second Window ICG</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>The primary study objective is to determine the diagnostic value of Second Window ICG (delayed, high dose IV administration of ICG) in the surgical resection of nervous system tumors.&#xD;
The first objective is to determine safety/efficacy of high dose, delayed indocyanine green (second window ICG) during surgery of nervous system tumors.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Optimal timing and dose of SWG</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>The second study objective is to calculate diagnostic test characteristics (sensitivity/specificity) of delayed, high dose indocyanine green (second window ICG) as a diagnostic aid during surgery of nervous system tumors.&#xD;
The third study objective is to optimize timing and dose of second window Indocyanine Green during surgery of nervous system tumors, based on sensitivity/specificity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Indocyanine Green</intervention_name>
    <description>Indocyanine Green</description>
    <arm_group_label>Diagnostic value of Second Window ICG</arm_group_label>
    <arm_group_label>Optimal timing and dose of SWG</arm_group_label>
    <other_name>ICG</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          1. Adult patients 18 years of age and older.&#xD;
&#xD;
          2. Patients presenting with a CNS tumor presumed to be resectable and are at risk for&#xD;
             local recurrence on pre-operative assessment&#xD;
&#xD;
          3. Good operative candidate as determined by the treating physician and multidisciplinary&#xD;
             team&#xD;
&#xD;
          4. Subject capable of giving informed consent and participating in the process of&#xD;
             consent.&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          1. Pregnant women as determined by urinary or serum beta hCG within 72 hours of surgery&#xD;
&#xD;
          2. Subjects with a history of iodide allergies&#xD;
&#xD;
          3. Vulnerable patient populations&#xD;
&#xD;
             a. Patients unable to participate in the consent process (children and neonates).&#xD;
&#xD;
          4. Patients with non-MRI compatible implanted metallic foreign bodies are excluded from&#xD;
             this study&quot;&#xD;
&#xD;
          5. Patients who due to severe claustrophobia cannot tolerate MRI scanning&quot;&#xD;
&#xD;
          6. Patients with a known allergy or hypersensitivity to MRI contrast agents including&#xD;
             gadolinium .&#xD;
&#xD;
          7. Patients with moderate to end-stage renal (kidney) disease, defined as a glomerular&#xD;
             filtration rate (GFR) less than 30 mL/day/1.73m2&#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>John Y.K. Lee, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>UPENN Neurosurgery</affiliation>
  </overall_official>
  <results_reference>
    <citation>Ostrom QT, Gittleman H, Liao P, Rouse C, Chen Y, Dowling J, Wolinsky Y, Kruchko C, Barnholtz-Sloan J. CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2007-2011. Neuro Oncol. 2014 Oct;16 Suppl 4(Suppl 4):iv1-63. doi: 10.1093/neuonc/nou223. No abstract available.</citation>
    <PMID>25304271</PMID>
  </results_reference>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>September 6, 2016</study_first_submitted>
  <study_first_submitted_qc>August 23, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 25, 2017</study_first_posted>
  <last_update_submitted>August 13, 2020</last_update_submitted>
  <last_update_submitted_qc>August 13, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 14, 2020</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>Neoplasms</mesh_term>
    <mesh_term>Brain Neoplasms</mesh_term>
    <mesh_term>Nervous System Neoplasms</mesh_term>
  </condition_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/NCT03262636
org study id: 0822231
nct id: NCT03262636
lead sponsor: 
has dmc: Yes
Primary malignant and non-malignant brain tumors account for an estimated 21.42 cases per
      100,000 for a total count of 343,175 incident tumors based on worldwide population estimates
      [1]. These entities result in variable but disappointing rates of survival, particularly for
      primary brain tumors (5-year survival rates: anaplastic astrocytoma 27%; glioblastoma
      multiforme 5%) [2, 3]. Metastatic brain tumors outnumber primary brain tumors (estimates as
      high as 10:1) as they affect approximately 25% of patients diagnosed with cancer [4-6]. In
      terms of brain tumor surgery, the extent of surgical resection-a factor that is greatly
      impacted by a Neurosurgeon's ability to visualize these tumors-is directly associated with
      patient outcomes and survival [7-9]. Although spinal cord tumors are lower in terms of their
      incidence [10], data correlating extent-of-resection to outcomes and survival have been
      demonstrated in patients with intramedullary tumors [11].

      Using systemically delivered compounds with a high sensitivity of detection by near-infrared
      (NIR) fluorescence, it would be possible for us to improve surgical resection thus minimizing
      chances of recurrence and improving survival. Simply, if the tumor cells will "glow" during
      surgery, the surgeons are more likely to identify tumor margins and residual disease, and
      are, therefore more likely to perform a superior cancer operation. By ensuring a negative
      margin through NIR imagery, it would make it possible to decrease the rates of recurrence and
      thus improve overall survival.

      This concept of intraoperative molecular imaging requires two innovations:

      (i) a fluorescent contrast agent that can be injected systemically into the subject and that
      selectively accumulates in the tumor tissues, and (ii) an imaging system that can detect and
      quantify the contrast agent in the tumor tissues.[12, 13]

      Subjects undergo intraoperative imaging, receiving an injection of indocyanine green and then
      undergoing intraoperative imaging of the surgery site with a NIR imaging system. The imaging
      devices allow the operating field to be observed in real-time.
Indocyanine green is a water-soluble tricarbocyanine dye routinely used in clinical settings
      for measuring cardiac output, hepatic function, liver blood flow and ophthalmic angiography
      and has been in use for over 60 years [14]. This protocol utilizes Patheon's indocyanine
      green, NDC 17238-424. The chemical formula is C45H47N2O6S2Na and the compound has a molecular
      weight of 774.96Da (CAS number 3599-32-4). It has a peak absorption in the NIR spectrum at
      800nm and maximal emission at 835nm. Indocyanine green is rapidly and completely bound to
      plasma proteins (especially albumin) after intravenous (IV) injection in the blood [15].

      Indocyanine Green for Injection USP is a sterile, lyophilized green powder containing 25 mg
      of indocyanine green with no more than 5% sodium iodide. It is packaged with Sterile Water
      for Injection, USP, which is used to dissolve the indocyanine green, and is to be
      administered intravenously
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Determining the sensitivity of ICG uptake and expression in identifying ANS tumor deposits when excited by an imaging probe.
time frame: 36 months
measure: optimize timing and dose of second window Indocyanine Green during surgery of nervous system tumors, based on sensitivity/specificity.
time frame: 36 months
arm group label: Diagnostic value of Second Window ICG
arm group type: Other
description: The primary study objective is to determine the diagnostic value of Second Window ICG (delayed, high dose IV administration of ICG) in the surgical resection of nervous system tumors.
The first objective is to determine safety/efficacy of high dose, delayed indocyanine green (second window ICG) during surgery of nervous system tumors.
arm group label: Optimal timing and dose of SWG
arm group type: Other
description: The second study objective is to calculate diagnostic test characteristics (sensitivity/specificity) of delayed, high dose indocyanine green (second window ICG) as a diagnostic aid during surgery of nervous system tumors.
The third study objective is to optimize timing and dose of second window Indocyanine Green during surgery of nervous system tumors, based on sensitivity/specificity.
intervention type: Drug
intervention name: Indocyanine Green
description: Indocyanine Green
arm group label: Diagnostic value of Second Window ICG
arm group label: Optimal timing and dose of SWG
other name: ICG
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: John Y.K. Lee, MD
role: Principal Investigator
affiliation: UPENN Neurosurgery
citation: Ostrom QT, Gittleman H, Liao P, Rouse C, Chen Y, Dowling J, Wolinsky Y, Kruchko C, Barnholtz-Sloan J. CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2007-2011. Neuro Oncol. 2014 Oct;16 Suppl 4(Suppl 4):iv1-63. doi: 10.1093/neuonc/nou223. No abstract available.
PMID: 25304271
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Brain Neoplasms
mesh term: Nervous System Neoplasms