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Ferumoxytol in Magnetic Resonance Imaging of Pediatric Patients With Brain Tumors

Primary Purpose

Brain Neoplasm

Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Ferumoxytol
Magnetic Resonance Imaging
Sponsored by
OHSU Knight Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Brain Neoplasm

Eligibility Criteria

5 Years - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Subjects with a presumed diagnosis of brain tumor (based on imaging) or a confirmed brain tumor (based on pathology) before or after any oncologic treatment (surgery/chemotherapy/radiation)
  • All subjects, or their legal guardians, must sign a written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization in accordance with institutional guidelines
  • Subjects with a calculated glomerular filtration rate (GFR) > 60 mL/min/1.73 m^2
  • Sexually active women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; surgical intervention i.e. tubal ligation or vasectomy; post-menopausal > 6 months or abstinence) for at least two months after each cycle of the study; should a female become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

Exclusion Criteria:

  • Subjects with clinically significant signs of uncal herniation, such as acute pupillary enlargement, rapidly developing motor changes (over hours), or rapidly decreasing level of consciousness, are not eligible
  • Subjects with known allergic or hypersensitivity reactions to parenteral iron, parenteral dextran, parenteral iron-dextran, or parenteral iron-polysaccharide preparations (Ferumoxytol Investigator's Drug Brochure, 2009); subjects with significant drug or other allergies or autoimmune diseases may be enrolled at the investigator's discretion
  • Subjects who are pregnant or lactating or who suspect they might be pregnant
  • Subjects who have a contraindication for 3Tesla (3T) MRI: metal in their bodies (a cardiac pacemaker or other incompatible device), are severely agitated, or have an allergy to gadolinium containing contrast material
  • Subjects with known iron overload (genetic hemochromatosis); in subjects with a family history of hemochromatosis, hemochromatosis must be ruled out prior to study entry with normal values of the following blood tests: transferrin saturation (TS) test and serum ferritin (SF) test; all associated costs will be paid by the study
  • Subject who have received ferumoxytol within 4 weeks of study entry

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Diagnostic (ferumoxytol, MRI)

    Arm 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.

    Outcomes

    Primary Outcome Measures

    Overlay accuracy with 3-dimensional anatomical T1w post contrast scans
    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.
    Confidence in identifying the lesion corresponding areas on cerebral blood volume maps
    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.
    Cerebral blood volume in small (< 1 cm) enhancing lesions
    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.
    Delineation of tumor from larger blood vessels
    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.

    Secondary Outcome Measures

    Relative cerebral blood volume value
    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.
    Treatment response
    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").
    Histology and genetic markers
    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.
    Ferumoxytol enhancement
    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).
    Survival
    Data will be collected for 5 years.
    Progression free survival
    Data will be collected for 5 years.

    Full Information

    First Posted
    July 26, 2017
    Last Updated
    November 3, 2021
    Sponsor
    OHSU Knight Cancer Institute
    Collaborators
    AMAG Pharmaceuticals, Inc., Oregon Health and Science University
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    1. Study Identification

    Unique Protocol Identification Number
    NCT03234309
    Brief Title
    Ferumoxytol in Magnetic Resonance Imaging of Pediatric Patients With Brain Tumors
    Official Title
    High Resolution Steady State Blood Volume Maps in Pediatric Brain Tumors Using MRI
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    November 2021
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    No enrollments
    Study Start Date
    October 20, 2017 (Actual)
    Primary Completion Date
    August 30, 2021 (Actual)
    Study Completion Date
    August 30, 2021 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    OHSU Knight Cancer Institute
    Collaborators
    AMAG Pharmaceuticals, Inc., Oregon Health and Science University

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    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.
    Detailed Description
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Brain Neoplasm

    7. Study Design

    Primary Purpose
    Diagnostic
    Study Phase
    Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Diagnostic (ferumoxytol, MRI)
    Arm Type
    Experimental
    Arm 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(s)
    Ferumoxytol
    Other Intervention Name(s)
    Feraheme, Ferumoxytol Non-Stoichiometric Magnetite
    Intervention Description
    Given IV
    Intervention Type
    Procedure
    Intervention Name(s)
    Magnetic Resonance Imaging
    Other Intervention Name(s)
    Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR Imaging, MRI, MRI Scan, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging
    Intervention Description
    Undergo MRI
    Primary Outcome Measure Information:
    Title
    Overlay accuracy with 3-dimensional anatomical T1w post contrast scans
    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.
    Time Frame
    Up to 5 years
    Title
    Confidence in identifying the lesion corresponding areas on cerebral blood volume maps
    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.
    Time Frame
    Up to 5 years
    Title
    Cerebral blood volume in small (< 1 cm) enhancing lesions
    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.
    Time Frame
    Up to 5 years
    Title
    Delineation of tumor from larger blood vessels
    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.
    Time Frame
    Up to 5 years
    Secondary Outcome Measure Information:
    Title
    Relative cerebral blood volume value
    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.
    Time Frame
    Up to 5 years
    Title
    Treatment response
    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").
    Time Frame
    Up to 5 years
    Title
    Histology and genetic markers
    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.
    Time Frame
    Up to 5 years
    Title
    Ferumoxytol enhancement
    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).
    Time Frame
    At 24 hours after administration
    Title
    Survival
    Description
    Data will be collected for 5 years.
    Time Frame
    Up to 5 years
    Title
    Progression free survival
    Description
    Data will be collected for 5 years.
    Time Frame
    Up to 5 years

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    5 Years
    Maximum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Subjects with a presumed diagnosis of brain tumor (based on imaging) or a confirmed brain tumor (based on pathology) before or after any oncologic treatment (surgery/chemotherapy/radiation) All subjects, or their legal guardians, must sign a written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization in accordance with institutional guidelines Subjects with a calculated glomerular filtration rate (GFR) > 60 mL/min/1.73 m^2 Sexually active women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; surgical intervention i.e. tubal ligation or vasectomy; post-menopausal > 6 months or abstinence) for at least two months after each cycle of the study; should a female become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately Exclusion Criteria: Subjects with clinically significant signs of uncal herniation, such as acute pupillary enlargement, rapidly developing motor changes (over hours), or rapidly decreasing level of consciousness, are not eligible Subjects with known allergic or hypersensitivity reactions to parenteral iron, parenteral dextran, parenteral iron-dextran, or parenteral iron-polysaccharide preparations (Ferumoxytol Investigator's Drug Brochure, 2009); subjects with significant drug or other allergies or autoimmune diseases may be enrolled at the investigator's discretion Subjects who are pregnant or lactating or who suspect they might be pregnant Subjects who have a contraindication for 3Tesla (3T) MRI: metal in their bodies (a cardiac pacemaker or other incompatible device), are severely agitated, or have an allergy to gadolinium containing contrast material Subjects with known iron overload (genetic hemochromatosis); in subjects with a family history of hemochromatosis, hemochromatosis must be ruled out prior to study entry with normal values of the following blood tests: transferrin saturation (TS) test and serum ferritin (SF) test; all associated costs will be paid by the study Subject who have received ferumoxytol within 4 weeks of study entry
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Edward A Neuwelt
    Organizational Affiliation
    OHSU Knight Cancer Institute
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Learn more about this trial

    Ferumoxytol in Magnetic Resonance Imaging of Pediatric Patients With Brain Tumors

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