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Steady State Blood Volume Maps Using Ferumoxytol Non-stoichiometric Magnetite MRI in Imaging Patients With Glioblastoma

Primary Purpose

Glioblastoma

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging

Ferumoxytol

Gadoteridol

Magnetic Resonance Imaging

About this trial

This is an interventional diagnostic trial for Glioblastoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Subjects must have a known or presumed radiological diagnosis of glioblastoma (GBM); for presumed diagnosis of GBM, histological confirmation of GBM must be completed within 12 weeks of enrollment; (subjects will be removed from study and non-evaluable if no histologic diagnosis of GBM is confirmed)
Subjects must be enrolled before starting chemoradiation, either pre -or post-surgery
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
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; 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 3 tesla (T) 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 3 weeks of study entry
Subjects with three or more drug allergies from separate drug classes

Sites / Locations

Ohio State University Comprehensive Cancer Center
OHSU Knight Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Diagnostic (DSC/DCE-CBV, SS-CBV mapping)

Arm Description

Patients receive 2 doses (2nd dose optional) of gadoteridol IV and undergo MRI including DSC or DCE-CBV mapping over approximately 45-60 minutes on day 1. Within 3 days, patients receive 3 doses of ferumoxytol non-stoichiometric magnetite IV and undergo MRI including DSC and SS-CBV mapping after each dose over approximately 90 minutes. Patients undergo MRI without contrast 24 hours after ferumoxytol non-stoichiometric magnetite over approximately 30 minutes. This 3 day series of imaging repeats at different stages of disease and may be performed up to 5 times: prior to surgery, prior to chemoradiation therapy, 4-6 weeks post-chemoradiation therapy, at time of progression on gadolinium MRI per RANO criteria, and again at time of progression (if the previous time of progression showed pseudoprogression).

Outcomes

Primary Outcome Measures

Assessment of overlay accuracy with 3-dimensional (3D) anatomical T1w post contrast scans (MPRAGE)

Will be analyzed and the mean score between the two readers will be used in the primary analyses. That is, to compare steady state-cerebral blood volume (SS-CBV) maps and dynamic susceptibility contrast (DSC)-CBV maps, a linear mixed effects model will be used to compare the mean of the visualization variables between SS and DSC overall and at each of time points (before chemoradiation, after chemoradiation, at progression and after second line treatment) while taking into account the correlation due to repeated measures, and the clustering within institutions. Model assumptions will be evaluated and alternative models will be explored as necessary.

Confidence in identifying the lesion corresponding areas on cerebral blood volume (CBV) maps

Will be analyzed and the mean score between the two readers will be used in the primary analyses. That is, to compare steady state (SS)-CBV maps and dynamic susceptibility contrast (DSC)-CBV maps, a linear mixed effects model will be used to compare the mean of the visualization variables between SS and DSC overall and at each of time points (before chemoradiation, after chemoradiation, at progression and after second line treatment) while taking into account the correlation due to repeated measures, and the clustering within institutions. Model assumptions will be evaluated and alternative models will be explored as necessary.

Assessment of cerebral blood volume (CBV) in small (< 1 cm) enhancing lesions

Delineation of tumor from larger blood vessels

Secondary Outcome Measures

Overall survival

For the assessment of therapeutic response and association with survival, the cerebral blood volume (CBV) values will be correlated with survival using a Cox mixed effects regression model while adjusting patient demographical and clinical characteristics and the clustering within institutions. To determine at which stage of the disease the steady state CBV will best predict survival as well as the best cut off points, separate models will be fit for different disease stages and different cutoff points including 1.75, others and the Response Assessment in Neuro-Oncology (RANO) criteria.

Relative cerebral blood volume (rCBV) values

A linear model will be used to assess correlation of rCBV with histology based on the availability of data.

Ferumoxytol enhancement

A linear mixed effects regression model will first be used to examine the relationship between transverse relaxation rate and ferumoxytol doses while taking the correlation due to repeated measures into account. If the relationship between transverse relaxation rate and ferumoxytol doses does not show good linearity, alternative function forms will be tested, for example, polynomial or exponential.

Full Information

NCT ID

NCT02359097

First Posted

February 4, 2015

Last Updated

March 11, 2022

Sponsor

OHSU Knight Cancer Institute

Collaborators

Oregon Health and Science University

1. Study Identification

Unique Protocol Identification Number

NCT02359097

Brief Title

Steady State Blood Volume Maps Using Ferumoxytol Non-stoichiometric Magnetite MRI in Imaging Patients With Glioblastoma

Official Title

High Resolution Steady State Blood Volume Maps in Glioblastoma Using MRI - A Multicenter Study

Study Type

Interventional

2. Study Status

Record Verification Date

March 2022

Overall Recruitment Status

Completed

Study Start Date

January 6, 2015 (Actual)

Primary Completion Date

March 12, 2021 (Actual)

Study Completion Date

March 12, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

OHSU Knight Cancer Institute

Collaborators

Oregon Health and Science University

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This clinical trial studies steady state blood volume maps using ferumoxytol non-stoichiometric magnetite magnetic resonance (MRI) in imaging patients with glioblastoma. MRI is a procedure in which radio waves and a powerful magnet linked to a computer are used to create detailed pictures of areas inside the body. Contrast agents, such as ferumoxytol non-stoichiometric magnetite, may enhance these pictures and increase visibility of tumor cells and the blood vessels in and around the tumors.

Detailed Description

PRIMARY OBJECTIVE: I. Testing if steady state (SS)-cerebral blood volume (CBV) maps are superior to dynamic susceptibility contrast-(DSC)-CBV maps in visualizing of brain tumor blood volumes. SECONDARY OBJECTIVES: I. Development of the SS-CBV mapping for quantitative CBV estimation. II. Assessment of therapeutic response. III. Association with survival. IV. Correlation of relative cerebral blood volume (rCBV) with histology. V. Assessment of late ferumoxytol (ferumoxytol non-stoichiometric magnetite) enhancement at various stages of disease. OUTLINE: Patients receive 2 doses (2nd dose optional) of gadoteridol intravenously (IV) and undergo MRI including DSC or dynamic contrast enhanced imaging (DCE)-CBV mapping over approximately 45-60 minutes on day 1. Within 3 days, patients receive 3 doses of ferumoxytol non-stoichiometric magnetite IV and undergo MRI including DSC and SS-CBV mapping after each dose over approximately 90 minutes. Patients undergo MRI without contrast 24 hours after ferumoxytol non-stoichiometric magnetite over approximately 30 minutes. This 2-3 day series of imaging repeats at different stages of disease and may be performed up to 5 times: prior to surgery, prior to chemoradiation therapy, 4-6 weeks post-chemoradiation therapy, at time of progression on gadolinium MRI per Response Assessment in Neuro-Oncology (RANO) criteria, and again at time of progression (if the previous time of progression showed pseudoprogression). After completion of study, patients are followed up at 2 and 6 weeks.

6. Conditions and Keywords

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

Glioblastoma

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

Outcomes Assessor

Masking Description

Radiologists will be blinded to the type of cerebral blood volume (CBV) maps (steady state [SS] and dynamic susceptibility contrast [DSC]) and patient information.

Allocation

N/A

Enrollment

29 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Diagnostic (DSC/DCE-CBV, SS-CBV mapping)

Arm Type

Experimental

Arm Description

Intervention Type

Procedure

Intervention Name(s)

Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging

Other Intervention Name(s)

DSC-MRI, Dynamic Susceptibility Contrast-Enhanced MRI, DYNAMIC SUSCEPTIBILITY-CONTRAST MRI

Intervention Description

Undergo MRI including DSC or DCE-CBV mapping

Intervention Type

Drug

Intervention Name(s)

Ferumoxytol

Other Intervention Name(s)

Feraheme, Ferumoxytol Non-Stoichiometric Magnetite

Intervention Description

Given IV

Intervention Type

Drug

Intervention Name(s)

Gadoteridol

Other Intervention Name(s)

Gadoteridolum, GD-HP-DO3A, HSDB 7549, ProHance, SQ 32692

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 including SS-CBV

Primary Outcome Measure Information:

Title

Assessment of overlay accuracy with 3-dimensional (3D) anatomical T1w post contrast scans (MPRAGE)

Description

Time Frame

Up to 6 weeks after last visit

Title

Confidence in identifying the lesion corresponding areas on cerebral blood volume (CBV) maps

Description

Time Frame

Up to 6 week after last visit

Title

Assessment of cerebral blood volume (CBV) in small (< 1 cm) enhancing lesions

Description

Time Frame

Up to 6 weeks after the last visit

Title

Delineation of tumor from larger blood vessels

Description

Time Frame

Up to 6 weeks after last visit

Secondary Outcome Measure Information:

Title

Overall survival

Description

Time Frame

Up to 6 weeks after last visit

Title

Relative cerebral blood volume (rCBV) values

Description

A linear model will be used to assess correlation of rCBV with histology based on the availability of data.

Time Frame

Up to 6 weeks after last visit

Title

Ferumoxytol enhancement

Description

Time Frame

24 hours after ferumoxytol administration

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Subjects must have a known or presumed radiological diagnosis of glioblastoma (GBM); for presumed diagnosis of GBM, histological confirmation of GBM must be completed within 12 weeks of enrollment; (subjects will be removed from study and non-evaluable if no histologic diagnosis of GBM is confirmed) Subjects must be enrolled before starting chemoradiation, either pre -or post-surgery 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 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; 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 3 tesla (T) 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 3 weeks of study entry Subjects with three or more drug allergies from separate drug classes

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Edward A Neuwelt

Organizational Affiliation

OHSU Knight Cancer Institute

Official's Role

Principal Investigator

Facility Information:

Facility Name

Ohio State University Comprehensive Cancer Center

City

Columbus

State/Province

Ohio

ZIP/Postal Code

43210

Country

United States

Facility Name

OHSU Knight Cancer Institute

City

Portland

State/Province

Oregon

ZIP/Postal Code

97239

Country

United States

12. IPD Sharing Statement

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Steady State Blood Volume Maps Using Ferumoxytol Non-stoichiometric Magnetite MRI in Imaging Patients With Glioblastoma

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