<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/NCT03270059</url>
  </required_header>
  <id_info>
    <org_study_id>STUDY00017028</org_study_id>
    <secondary_id>NCI-2017-01460</secondary_id>
    <secondary_id>STUDY00017028</secondary_id>
    <nct_id>NCT03270059</nct_id>
  </id_info>
  <brief_title>Gadolinium and Ferumoxytol MRI in Diagnosing Patients With Abnormalities in the Central Nervous System</brief_title>
  <official_title>The Feasibility of Steady State CBV Mapping Using Ferumoxytol Immediately After Gadolinium Enhanced MRI of the CNS</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>OHSU Knight Cancer Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Celgene Corporation</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase II trial studies how well gadolinium and ferumoxytol magnetic resonance imaging&#xD;
      (MRI) work in diagnosing patients with abnormalities in the central nervous system.&#xD;
      Diagnostic procedures, such as gadolinium and ferumoxytol MRI, may help find and diagnose&#xD;
      abnormalities in the central nervous system.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To test if prior gadolinium administration affects vascular imaging using ferumoxytol.&#xD;
&#xD;
      II. To test signal changes of T2*w multi-echo fast field echo (mFFE) scans before and after&#xD;
      contrast agent injection.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To test if ferumoxytol affects gadolinium enhanced MRI. II. To test if steady state&#xD;
      cerebral blood volume (CBV) maps are different at various magnetic field strengths.&#xD;
&#xD;
      EXPLORATORY OBJECTIVES:&#xD;
&#xD;
      I. To explore late ferumoxytol enhancement (optional MRI) hours to days after ferumoxytol&#xD;
      administration in various brain pathologies.&#xD;
&#xD;
      II. To evaluate the effects of ferumoxytol on malignant and non-malignant lesions in head &amp;&#xD;
      neck, and liver lesions&#xD;
&#xD;
      OUTLINE: Patients are randomized into 1 of 2 groups.&#xD;
&#xD;
      GROUP I: Patients receive gadolinium intravenously (IV) and then ferumoxytol IV and undergo&#xD;
      MRI over 60 minutes on day 1.&#xD;
&#xD;
      GROUP II: Patients receive ferumoxytol IV and then gadolinium IV and undergo MRI over 60&#xD;
      minutes on day 1.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 6, 2017</start_date>
  <completion_date type="Anticipated">August 15, 2026</completion_date>
  <primary_completion_date type="Anticipated">August 15, 2025</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Visualization of normal vasculature</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Primary analysis will use the average score of the two readers. The mean difference and the associated 95% confidence interval (CI) between the two groups will be estimated using a linear regression model. Equivalence will be claimed if the 95% CI does not include 0.4 on either side (equivalence margin is 0.4).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Visualization of abnormal vasculature</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Primary analysis will use the average score of the two readers. The mean difference and the associated 95% CI between the two groups will be estimated using a linear regression model. Equivalence will be claimed if the 95% CI does not include 0.4 on either side (equivalence margin is 0.4).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Visualization of normal anatomical structures</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Primary analysis will use the average score of the two readers. The mean difference and the associated 95% CI between the two groups will be estimated using a linear regression model. Equivalence will be claimed if the 95% CI does not include 0.4 on either side (equivalence margin is 0.4).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Identification of the lesion corresponding areas on cerebral blood volume (CBV) maps</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Will assess the confidence in identifying the lesion corresponding areas on CBV maps as well as signal change (deltaR2*) and relative cerebral blood volume. Primary analysis will use the average score of the two readers. The mean difference and the associated 95% CI between the two groups will be estimated using a linear regression model. Equivalence will be claimed if the 95% CI does not include 0.4 on either side (equivalence margin is 0.4).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Contrast enhancement</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>The mean difference and the associated 95% CI before versus after ferumoxytol in the three visualization variables will be estimated using a paired t-test based on the average score of the two readers. Will use the same equivalence margin of 0.4. To compare the two magnetic field strengths, will also use a linear regression model to analyze contrast to noise ratios, Image homogeneity and susceptibility artifacts (the latter two based on average score of the two readers).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Border delineation</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>The mean difference and the associated 95% CI before versus after ferumoxytol in the three visualization variables will be estimated using a paired t-test based on the average score of the two readers. Will use the same equivalence margin of 0.4. To compare the two magnetic field strengths, will also use a linear regression model to analyze contrast to noise ratios, Image homogeneity and susceptibility artifacts (the latter two based on average score of the two readers).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Internal morphology</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>The mean difference and the associated 95% CI before versus after ferumoxytol in the three visualization variables will be estimated using a paired t-test based on the average score of the two readers. Will use the same equivalence margin of 0.4. To compare the two magnetic field strengths, will also use a linear regression model to analyze contrast to noise ratios, Image homogeneity and susceptibility artifacts (the latter two based on average score of the two readers).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">150</enrollment>
  <condition>Central Nervous System Neoplasm</condition>
  <condition>Cranial Nerve Disorder</condition>
  <condition>Metastatic Malignant Neoplasm in the Brain</condition>
  <arm_group>
    <arm_group_label>Group I (gadolinium, ferumoxytol, MRI)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive gadolinium IV and then ferumoxytol IV and undergo MRI over 60 minutes on day 1.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group II (ferumoxytol, gadolinium, MRI)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive ferumoxytol IV and then gadolinium IV and undergo MRI over 60 minutes on day 1.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ferumoxytol</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Group I (gadolinium, ferumoxytol, MRI)</arm_group_label>
    <arm_group_label>Group II (ferumoxytol, gadolinium, MRI)</arm_group_label>
    <other_name>Feraheme</other_name>
    <other_name>Ferumoxytol Non-Stoichiometric Magnetite</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gadolinium</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Group I (gadolinium, ferumoxytol, MRI)</arm_group_label>
    <arm_group_label>Group II (ferumoxytol, gadolinium, MRI)</arm_group_label>
    <other_name>Gd</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Magnetic Resonance Imaging</intervention_name>
    <description>Undergo MRI</description>
    <arm_group_label>Group I (gadolinium, ferumoxytol, MRI)</arm_group_label>
    <arm_group_label>Group II (ferumoxytol, gadolinium, 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 must have one of the following:&#xD;
&#xD;
               -  Neurological findings (i.e. headache, loss of consciousness, paresis, cranial&#xD;
                  neuropathy, seizures, etc.)&#xD;
&#xD;
               -  Radiological abnormalities in the brain (neoplastic or non-neoplastic in nature)&#xD;
&#xD;
               -  Neoplastic process elsewhere in the body that may affect the brain (i.e. possible&#xD;
                  metastasis, vascular compromise, treatment related changes, etc.)&#xD;
&#xD;
          -  Subjects must be able to undergo MRI imaging without anesthesia&#xD;
&#xD;
          -  Subjects must be at least 10 years of age&#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;
          -  Sexually active women of child-bearing potential 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 &lt; 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 MRI: metal in their bodies (a cardiac&#xD;
             pacemaker or other incompatible device), are severely agitated, or have an allergy to&#xD;
             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 3 weeks of study entry&#xD;
&#xD;
          -  Subjects with three or more drug allergies from separate drug classes&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>10 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michael F Regner</last_name>
    <role>Principal Investigator</role>
    <affiliation>OHSU Knight Cancer Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>OHSU Knight Cancer Institute</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Michael F Regner</last_name>
      <phone>503-418-0990</phone>
      <email>regnerm@ohsu.edu</email>
    </contact>
    <investigator>
      <last_name>Michael F Regner</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>August 30, 2017</study_first_submitted>
  <study_first_submitted_qc>August 30, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 1, 2017</study_first_posted>
  <last_update_submitted>August 24, 2023</last_update_submitted>
  <last_update_submitted_qc>August 24, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 28, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>OHSU Knight Cancer Institute</investigator_affiliation>
    <investigator_full_name>Michael F. Regner, M.D., M.S.</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>Neoplasms</mesh_term>
    <mesh_term>Nervous System Neoplasms</mesh_term>
    <mesh_term>Central Nervous System Neoplasms</mesh_term>
    <mesh_term>Cranial Nerve Diseases</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/NCT03270059
org study id: STUDY00017028
secondary id: NCI-2017-01460
secondary id: STUDY00017028
nct id: NCT03270059
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This phase II trial studies how well gadolinium and ferumoxytol magnetic resonance imaging
      (MRI) work in diagnosing patients with abnormalities in the central nervous system.
      Diagnostic procedures, such as gadolinium and ferumoxytol MRI, may help find and diagnose
      abnormalities in the central nervous system.
PRIMARY OBJECTIVES:

      I. To test if prior gadolinium administration affects vascular imaging using ferumoxytol.

      II. To test signal changes of T2*w multi-echo fast field echo (mFFE) scans before and after
      contrast agent injection.

      SECONDARY OBJECTIVES:

      I. To test if ferumoxytol affects gadolinium enhanced MRI. II. To test if steady state
      cerebral blood volume (CBV) maps are different at various magnetic field strengths.

      EXPLORATORY OBJECTIVES:

      I. To explore late ferumoxytol enhancement (optional MRI) hours to days after ferumoxytol
      administration in various brain pathologies.

      II. To evaluate the effects of ferumoxytol on malignant and non-malignant lesions in head &
      neck, and liver lesions

      OUTLINE: Patients are randomized into 1 of 2 groups.

      GROUP I: Patients receive gadolinium intravenously (IV) and then ferumoxytol IV and undergo
      MRI over 60 minutes on day 1.

      GROUP II: Patients receive ferumoxytol IV and then gadolinium IV and undergo MRI over 60
      minutes on day 1.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: Single (Outcomes Assessor)
measure: Visualization of normal vasculature
time frame: Up to 5 years
description: Primary analysis will use the average score of the two readers. The mean difference and the associated 95% confidence interval (CI) between the two groups will be estimated using a linear regression model. Equivalence will be claimed if the 95% CI does not include 0.4 on either side (equivalence margin is 0.4).
measure: Visualization of abnormal vasculature
time frame: Up to 5 years
description: Primary analysis will use the average score of the two readers. The mean difference and the associated 95% CI between the two groups will be estimated using a linear regression model. Equivalence will be claimed if the 95% CI does not include 0.4 on either side (equivalence margin is 0.4).
measure: Visualization of normal anatomical structures
time frame: Up to 5 years
description: Primary analysis will use the average score of the two readers. The mean difference and the associated 95% CI between the two groups will be estimated using a linear regression model. Equivalence will be claimed if the 95% CI does not include 0.4 on either side (equivalence margin is 0.4).
measure: Identification of the lesion corresponding areas on cerebral blood volume (CBV) maps
time frame: Up to 5 years
description: Will assess the confidence in identifying the lesion corresponding areas on CBV maps as well as signal change (deltaR2*) and relative cerebral blood volume. Primary analysis will use the average score of the two readers. The mean difference and the associated 95% CI between the two groups will be estimated using a linear regression model. Equivalence will be claimed if the 95% CI does not include 0.4 on either side (equivalence margin is 0.4).
measure: Contrast enhancement
time frame: Up to 5 years
description: The mean difference and the associated 95% CI before versus after ferumoxytol in the three visualization variables will be estimated using a paired t-test based on the average score of the two readers. Will use the same equivalence margin of 0.4. To compare the two magnetic field strengths, will also use a linear regression model to analyze contrast to noise ratios, Image homogeneity and susceptibility artifacts (the latter two based on average score of the two readers).
measure: Border delineation
time frame: Up to 5 years
description: The mean difference and the associated 95% CI before versus after ferumoxytol in the three visualization variables will be estimated using a paired t-test based on the average score of the two readers. Will use the same equivalence margin of 0.4. To compare the two magnetic field strengths, will also use a linear regression model to analyze contrast to noise ratios, Image homogeneity and susceptibility artifacts (the latter two based on average score of the two readers).
measure: Internal morphology
time frame: Up to 5 years
description: The mean difference and the associated 95% CI before versus after ferumoxytol in the three visualization variables will be estimated using a paired t-test based on the average score of the two readers. Will use the same equivalence margin of 0.4. To compare the two magnetic field strengths, will also use a linear regression model to analyze contrast to noise ratios, Image homogeneity and susceptibility artifacts (the latter two based on average score of the two readers).
arm group label: Group I (gadolinium, ferumoxytol, MRI)
arm group type: Experimental
description: Patients receive gadolinium IV and then ferumoxytol IV and undergo MRI over 60 minutes on day 1.
arm group label: Group II (ferumoxytol, gadolinium, MRI)
arm group type: Experimental
description: Patients receive ferumoxytol IV and then gadolinium IV and undergo MRI over 60 minutes on day 1.
intervention type: Drug
intervention name: Ferumoxytol
description: Given IV
arm group label: Group I (gadolinium, ferumoxytol, MRI)
arm group label: Group II (ferumoxytol, gadolinium, MRI)
other name: Feraheme
other name: Ferumoxytol Non-Stoichiometric Magnetite
intervention type: Drug
intervention name: Gadolinium
description: Given IV
arm group label: Group I (gadolinium, ferumoxytol, MRI)
arm group label: Group II (ferumoxytol, gadolinium, MRI)
other name: Gd
intervention type: Procedure
intervention name: Magnetic Resonance Imaging
description: Undergo MRI
arm group label: Group I (gadolinium, ferumoxytol, MRI)
arm group label: Group II (ferumoxytol, gadolinium, 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: 10 Years
maximum age: N/A
healthy volunteers: No
last name: Michael F Regner
role: Principal Investigator
affiliation: OHSU Knight Cancer Institute
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: OHSU Knight Cancer Institute
investigator full name: Michael F. Regner, M.D., M.S.
investigator title: Principal Investigator
mesh term: Neoplasms
mesh term: Nervous System Neoplasms
mesh term: Central Nervous System Neoplasms
mesh term: Cranial Nerve Diseases
mesh term: Ferrosoferric Oxide