<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/NCT03234309</url>
  </required_header>
  <id_info>
    <org_study_id>STUDY00016165</org_study_id>
    <secondary_id>NCI-2017-00713</secondary_id>
    <secondary_id>STUDY00016165</secondary_id>
    <nct_id>NCT03234309</nct_id>
  </id_info>
  <brief_title>Ferumoxytol in Magnetic Resonance Imaging of Pediatric Patients With Brain Tumors</brief_title>
  <official_title>High Resolution Steady State Blood Volume Maps in Pediatric Brain Tumors Using MRI</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>OHSU Knight Cancer Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AMAG Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Oregon Health and Science University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>OHSU Knight Cancer Institute</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase II trial studies ferumoxytol in the magnetic resonance imaging of pediatric&#xD;
      patients with brain tumors. Magnetic resonance imaging using ferumoxytol may help in viewing&#xD;
      a brain tumor and blood vessels in and around the tumor in a different way than the standard&#xD;
      gadolinium-based contrast agent. Imaging with this experimental contrast agent may give&#xD;
      doctors more information about tumor blood supply and the extent of the tumor itself.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVE:&#xD;
&#xD;
      I. Testing the superiority of ferumoxytol-based steady state (SS)-cerebral blood volume (CBV)&#xD;
      maps over gadolinium-based contrast agent (GBCA)-based dynamic susceptibility weighted&#xD;
      (DSC)-CBV maps in visualizing pediatric brain tumor blood volume maps.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. Correlation of relative cerebral blood volume (rCBV) with histology and genetic markers.&#xD;
&#xD;
      II. Assessment of therapeutic response. III. Assessment of late ferumoxytol enhancement at&#xD;
      various stages of disease.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients undergo magnetic resonance imaging (MRI) with GBCA per standard of care over 45-60&#xD;
      minutes and then receive ferumoxytol intravenously (IV) followed by MRI over 10 minutes on&#xD;
      day 1. Patients may optionally undergo MRI over 30 minutes without any contrast agent on day&#xD;
      2. Each study visit consisting of 2 days may repeat no more frequently than 4 weeks for up to&#xD;
      5 study visits at different stages of the disease as determined by the investigator.&#xD;
&#xD;
      After completion of study, patients are followed up at 2 and 6 weeks and then periodically&#xD;
      for 5 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    No enrollments&#xD;
  </why_stopped>
  <start_date type="Actual">October 20, 2017</start_date>
  <completion_date type="Actual">August 30, 2021</completion_date>
  <primary_completion_date type="Actual">August 30, 2021</primary_completion_date>
  <phase>Phase 2</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>Overlay accuracy with 3-dimensional anatomical T1w post contrast scans</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Ferumoxytol-based steady state-cerebral blood volume maps will be compared to gadolinium-based dynamic susceptibility weighted-cerebral blood volume maps using a 3-point scale. The mean score between the two readers will be used in the primary analyses. Inter-reader agreement will be assessed using weighted Kappa to make sure that the visualization variables are used reliably.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Confidence in identifying the lesion corresponding areas on cerebral blood volume maps</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>The mean score between the two readers will be used in the primary analyses. A linear mixed effects model will be used to compare the mean of the four visualization variables between steady state and dynamic susceptibility weighted overall and at each of time points while taking into account the correlation due to repeated measures within the same patient. Inter-reader agreement will be assessed using weighted Kappa to make sure that the visualization variables are used reliably.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cerebral blood volume in small (&lt; 1 cm) enhancing lesions</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Ferumoxytol-based steady state-cerebral blood volume maps will be compared to gadolinium-based dynamic susceptibility weighted-cerebral blood volume maps using a 3-point scale.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Delineation of tumor from larger blood vessels</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Ferumoxytol-based steady state-cerebral blood volume maps will be compared to gadolinium-based dynamic susceptibility weighted-cerebral blood volume maps using a 3-point scale. The mean score between the two readers will be used in the primary analyses. Inter-reader agreement will be assessed using weighted Kappa to make sure that the visualization variables are used reliably.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Relative cerebral blood volume value</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Sensitivity and specificity of relative cerebral blood volume will be calculated for identifying true disease progression at different cutoff points and compare the performance between steady state and dynamic susceptibility weighted maps using McNemar's tests, and using a mixed effect logistic regression model to look at all data across different disease stages (within the same patient) if necessary and allowed by available data.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment response</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>For the assessment of therapeutic response, enhancing areas will be categorized as active tumor or therapy related changes based on relative cerebral blood volume values. Different cutoff points (e.g. 1.5, 1.75 and 2) will be tested for relative cerebral blood volume value from both steady state and dynamic susceptibility weighted maps, and disease status will be confirmed with subsequent magnetic resonance imaging results as recommended by Response Assessment in Neuro-Oncology Criteria or histopathology from additional surgeries (&quot;gold standard&quot;).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Histology and genetic markers</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>A linear model will be used to assess correlation of relative cerebral blood volume with histology and genetic markers based on the availability of data and type of tumor.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ferumoxytol enhancement</measure>
    <time_frame>At 24 hours after administration</time_frame>
    <description>Similar models to those for primary objectives will evaluate late ferumoxytol enhancement at various stages of disease. Will be assessed on T1 and T2 weighted magnetic resonance (MR) sequences. Enhancement changes including intensity and pattern (heterogeneity) at various stages of disease will be analyzed and compared to gadolinium based contrast agent (GBCA).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Survival</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Data will be collected for 5 years.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Data will be collected for 5 years.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Brain Neoplasm</condition>
  <arm_group>
    <arm_group_label>Diagnostic (ferumoxytol, MRI)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients undergo MRI with GBCA per standard of care over 45-60 minutes and then receive ferumoxytol IV followed by MRI over 10 minutes on day 1. Patients may optionally undergo MRI over 30 minutes without any contrast agent on day 2. Each study visit consisting of 2 days may repeat no more frequently than 4 weeks for up to 5 study visits at different stages of the disease as determined by the investigator.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ferumoxytol</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Diagnostic (ferumoxytol, MRI)</arm_group_label>
    <other_name>Feraheme</other_name>
    <other_name>Ferumoxytol Non-Stoichiometric Magnetite</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Magnetic Resonance Imaging</intervention_name>
    <description>Undergo MRI</description>
    <arm_group_label>Diagnostic (ferumoxytol, MRI)</arm_group_label>
    <other_name>Magnetic Resonance Imaging Scan</other_name>
    <other_name>Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance</other_name>
    <other_name>MR Imaging</other_name>
    <other_name>MRI</other_name>
    <other_name>MRI Scan</other_name>
    <other_name>NMR Imaging</other_name>
    <other_name>NMRI</other_name>
    <other_name>Nuclear Magnetic Resonance Imaging</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects with a presumed diagnosis of brain tumor (based on imaging) or a confirmed&#xD;
             brain tumor (based on pathology) before or after any oncologic treatment&#xD;
             (surgery/chemotherapy/radiation)&#xD;
&#xD;
          -  All subjects, or their legal guardians, must sign a written informed consent and&#xD;
             Health Insurance Portability and Accountability Act (HIPAA) authorization in&#xD;
             accordance with institutional guidelines&#xD;
&#xD;
          -  Subjects with a calculated glomerular filtration rate (GFR) &gt; 60 mL/min/1.73 m^2&#xD;
&#xD;
          -  Sexually active women of child-bearing potential and men must agree to use adequate&#xD;
             contraception (hormonal or barrier method of birth control; surgical intervention i.e.&#xD;
             tubal ligation or vasectomy; post-menopausal &gt; 6 months or abstinence) for at least&#xD;
             two months after each cycle of the study; should a female become pregnant or suspect&#xD;
             she is pregnant while participating in this study, she should inform her treating&#xD;
             physician immediately&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects with clinically significant signs of uncal herniation, such as acute&#xD;
             pupillary enlargement, rapidly developing motor changes (over hours), or rapidly&#xD;
             decreasing level of consciousness, are not eligible&#xD;
&#xD;
          -  Subjects with known allergic or hypersensitivity reactions to parenteral iron,&#xD;
             parenteral dextran, parenteral iron-dextran, or parenteral iron-polysaccharide&#xD;
             preparations (Ferumoxytol Investigator's Drug Brochure, 2009); subjects with&#xD;
             significant drug or other allergies or autoimmune diseases may be enrolled at the&#xD;
             investigator's discretion&#xD;
&#xD;
          -  Subjects who are pregnant or lactating or who suspect they might be pregnant&#xD;
&#xD;
          -  Subjects who have a contraindication for 3Tesla (3T) MRI: metal in their bodies (a&#xD;
             cardiac pacemaker or other incompatible device), are severely agitated, or have an&#xD;
             allergy to gadolinium containing contrast material&#xD;
&#xD;
          -  Subjects with known iron overload (genetic hemochromatosis); in subjects with a family&#xD;
             history of hemochromatosis, hemochromatosis must be ruled out prior to study entry&#xD;
             with normal values of the following blood tests: transferrin saturation (TS) test and&#xD;
             serum ferritin (SF) test; all associated costs will be paid by the study&#xD;
&#xD;
          -  Subject who have received ferumoxytol within 4 weeks of study entry&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>5 Years</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Edward A Neuwelt</last_name>
    <role>Principal Investigator</role>
    <affiliation>OHSU Knight Cancer Institute</affiliation>
  </overall_official>
  <removed_countries>
    <country>United States</country>
  </removed_countries>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>July 26, 2017</study_first_submitted>
  <study_first_submitted_qc>July 26, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 31, 2017</study_first_posted>
  <last_update_submitted>November 3, 2021</last_update_submitted>
  <last_update_submitted_qc>November 3, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 10, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>OHSU Knight Cancer Institute</investigator_affiliation>
    <investigator_full_name>Edward Neuwelt</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brain Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ferrosoferric Oxide</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/NCT03234309
org study id: STUDY00016165
secondary id: NCI-2017-00713
secondary id: STUDY00016165
nct id: NCT03234309
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This phase II trial studies ferumoxytol in the magnetic resonance imaging of pediatric
      patients with brain tumors. Magnetic resonance imaging using ferumoxytol may help in viewing
      a brain tumor and blood vessels in and around the tumor in a different way than the standard
      gadolinium-based contrast agent. Imaging with this experimental contrast agent may give
      doctors more information about tumor blood supply and the extent of the tumor itself.
PRIMARY OBJECTIVE:

      I. Testing the superiority of ferumoxytol-based steady state (SS)-cerebral blood volume (CBV)
      maps over gadolinium-based contrast agent (GBCA)-based dynamic susceptibility weighted
      (DSC)-CBV maps in visualizing pediatric brain tumor blood volume maps.

      SECONDARY OBJECTIVES:

      I. Correlation of relative cerebral blood volume (rCBV) with histology and genetic markers.

      II. Assessment of therapeutic response. III. Assessment of late ferumoxytol enhancement at
      various stages of disease.

      OUTLINE:

      Patients undergo magnetic resonance imaging (MRI) with GBCA per standard of care over 45-60
      minutes and then receive ferumoxytol intravenously (IV) followed by MRI over 10 minutes on
      day 1. Patients may optionally undergo MRI over 30 minutes without any contrast agent on day
      2. Each study visit consisting of 2 days may repeat no more frequently than 4 weeks for up to
      5 study visits at different stages of the disease as determined by the investigator.

      After completion of study, patients are followed up at 2 and 6 weeks and then periodically
      for 5 years.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Overlay accuracy with 3-dimensional anatomical T1w post contrast scans
time frame: Up to 5 years
description: Ferumoxytol-based steady state-cerebral blood volume maps will be compared to gadolinium-based dynamic susceptibility weighted-cerebral blood volume maps using a 3-point scale. The mean score between the two readers will be used in the primary analyses. Inter-reader agreement will be assessed using weighted Kappa to make sure that the visualization variables are used reliably.
measure: Confidence in identifying the lesion corresponding areas on cerebral blood volume maps
time frame: Up to 5 years
description: The mean score between the two readers will be used in the primary analyses. A linear mixed effects model will be used to compare the mean of the four visualization variables between steady state and dynamic susceptibility weighted overall and at each of time points while taking into account the correlation due to repeated measures within the same patient. Inter-reader agreement will be assessed using weighted Kappa to make sure that the visualization variables are used reliably.
measure: Cerebral blood volume in small (< 1 cm) enhancing lesions
time frame: Up to 5 years
description: Ferumoxytol-based steady state-cerebral blood volume maps will be compared to gadolinium-based dynamic susceptibility weighted-cerebral blood volume maps using a 3-point scale.
measure: Delineation of tumor from larger blood vessels
time frame: Up to 5 years
description: Ferumoxytol-based steady state-cerebral blood volume maps will be compared to gadolinium-based dynamic susceptibility weighted-cerebral blood volume maps using a 3-point scale. The mean score between the two readers will be used in the primary analyses. Inter-reader agreement will be assessed using weighted Kappa to make sure that the visualization variables are used reliably.
measure: Relative cerebral blood volume value
time frame: Up to 5 years
description: Sensitivity and specificity of relative cerebral blood volume will be calculated for identifying true disease progression at different cutoff points and compare the performance between steady state and dynamic susceptibility weighted maps using McNemar's tests, and using a mixed effect logistic regression model to look at all data across different disease stages (within the same patient) if necessary and allowed by available data.
measure: Treatment response
time frame: Up to 5 years
description: For the assessment of therapeutic response, enhancing areas will be categorized as active tumor or therapy related changes based on relative cerebral blood volume values. Different cutoff points (e.g. 1.5, 1.75 and 2) will be tested for relative cerebral blood volume value from both steady state and dynamic susceptibility weighted maps, and disease status will be confirmed with subsequent magnetic resonance imaging results as recommended by Response Assessment in Neuro-Oncology Criteria or histopathology from additional surgeries ("gold standard").
measure: Histology and genetic markers
time frame: Up to 5 years
description: A linear model will be used to assess correlation of relative cerebral blood volume with histology and genetic markers based on the availability of data and type of tumor.
measure: Ferumoxytol enhancement
time frame: At 24 hours after administration
description: Similar models to those for primary objectives will evaluate late ferumoxytol enhancement at various stages of disease. Will be assessed on T1 and T2 weighted magnetic resonance (MR) sequences. Enhancement changes including intensity and pattern (heterogeneity) at various stages of disease will be analyzed and compared to gadolinium based contrast agent (GBCA).
measure: Survival
time frame: Up to 5 years
description: Data will be collected for 5 years.
measure: Progression free survival
time frame: Up to 5 years
description: Data will be collected for 5 years.
arm group label: Diagnostic (ferumoxytol, MRI)
arm group type: Experimental
description: Patients undergo MRI with GBCA per standard of care over 45-60 minutes and then receive ferumoxytol IV followed by MRI over 10 minutes on day 1. Patients may optionally undergo MRI over 30 minutes without any contrast agent on day 2. Each study visit consisting of 2 days may repeat no more frequently than 4 weeks for up to 5 study visits at different stages of the disease as determined by the investigator.
intervention type: Drug
intervention name: Ferumoxytol
description: Given IV
arm group label: Diagnostic (ferumoxytol, MRI)
other name: Feraheme
other name: Ferumoxytol Non-Stoichiometric Magnetite
intervention type: Procedure
intervention name: Magnetic Resonance Imaging
description: Undergo MRI
arm group label: Diagnostic (ferumoxytol, MRI)
other name: Magnetic Resonance Imaging Scan
other name: Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
other name: MR Imaging
other name: MRI
other name: MRI Scan
other name: NMR Imaging
other name: NMRI
other name: Nuclear Magnetic Resonance Imaging
criteria: 
gender: All
minimum age: 5 Years
maximum age: 18 Years
healthy volunteers: No
last name: Edward A Neuwelt
role: Principal Investigator
affiliation: OHSU Knight Cancer Institute
country: United States
responsible party type: Principal Investigator
investigator affiliation: OHSU Knight Cancer Institute
investigator full name: Edward Neuwelt
investigator title: Principal Investigator
mesh term: Brain Neoplasms
mesh term: Ferrosoferric Oxide