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Ferumoxytol- and Gadolinium-Labeled MRI in Measuring Tumors Before or After Treatment in Patients With Primary or Metastatic Brain Tumors

Primary Purpose

Metastatic Malignant Neoplasm in the Brain, Primary Brain Neoplasm

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

3 Tesla Magnetic Resonance Imaging

Dynamic Contrast-Enhanced Magnetic Resonance Imaging

Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging

Ferumoxytol

Gadolinium

High Field Strength Magnetic Resonance Imaging

Susceptibility Weighted Imaging

About this trial

This is an interventional diagnostic trial for Metastatic Malignant Neoplasm in the Brain

Eligibility Criteria

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

Inclusion Criteria:

Subjects with radiographically suspected, histologically or cytologically confirmed primary brain tumors or brain metastasis are eligible
Subjects may be enrolled at any point in diagnosis or treatment
Subjects must have had radiographically evaluable or measurable disease with standard magnetic resonance (MR) imaging
Members of all races and ethnic groups will be included
Eastern Cooperative Oncology Group (ECOG) performance status =< 3 (Karnofsky performance status [KPS] >= 30)
Ability to understand and the willingness to sign a written informed consent document, or have a representative able to consent for the subject
Sexually active women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; or abstinence) prior to study treatment and for the duration of study treatment; should a female become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
Subject agrees to complete follow up visit

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
Subjects who have a contraindication for MRI: metal in their bodies (a cardiac pacemaker or other incompatible device), are severely agitated, need monitored anesthesia for scanning, or have an allergy to Gd contrast material
Subjects with known hepatic insufficiency or cirrhosis
History of allergic reactions attributed to compounds of similar chemical or biologic composition to ferumoxytol
Subjects with known or suspected iron overload (genetic hemochromatosis or history of multiple transfusions)
Subjects expecting to undergo surgery between the imaging sessions; subjects may undergo surgery at any time before the first, or after the last imaging session; this exclusion only applies to each study visit (3 day scanning session), and does not apply to the time (at least 3 weeks) between each study visit
Uncontrolled concurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Pregnant or lactating women are excluded from this study
Inability or unwillingness to undergo the complete series of imaging sessions; inability or unwillingness to complete the one month follow-up
Human immunodeficiency virus (HIV)-positive subjects on combination antiretroviral therapy are ineligible
Subjects with glomerular filtration rate (GFR) < 50
Subjects with three or more drug allergies from separate drug classes

Sites / Locations

OHSU Knight Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Diagnostic (Gd, ferumoxytol, 3T or 7T MRI)

Arm Description

Patients receive gadolinium IV on day 1 and ferumoxytol non-stoichiometric magnetite IV on day 2. Patients undergo anatomical MRI sequences with 3T or 7T at baseline and on days 1-3. Patients also undergo DSC MRI and DCE MRI on days 1-2. Day 1 and day 2 imaging sessions may be separated by up to 7 days.

Outcomes

Primary Outcome Measures

Contrast to Noise Ratio (CNR), in Terms of Normalized Signal Intensity Changes, for T1-weighted MRI Signal at 3T and 7T (Gadolinium [Gd] T1-weighted Magnetic Resonance Imaging [MRI] DCE Data Only)

Paired sample t-tests will be used for primary descriptive comparisons. Secondary analyses will use a repeated measures analysis of variance (ANOVA) model to compare 3T and 7T while adjusting for other factors including tumor type, prior therapy, and, potentially, important baseline factors that differ between the subjects assigned to the two field strengths. Normality will be assessed graphically and, if needed, a transformation (e.g. the logarithmic transform) will be applied.

CNR, in Terms of Normalized Signal Intensity Changes, for Dynamic Susceptibility Contrast (DSC) MRI Data Sets at 3T and 7T (Gadolinium and Ferumoxytol)

A two sample t-test was used for primary descriptive comparisons since CNR was measured on different subjects at 3T and 7T. There were no repeated measures in the resulting data. Given the small sample size, a linear regression was conducted to compare CNR between 3T and 7T only adjusted for Fe dose. No other adjusted analyses were conducted. CNR was compared between 3T and 7T for both Ferumoxytol and Gadolinum. Ferumoxytol was administered using three injections and CNR was measured after each injection, thus we have three measures of CNR (Fe1CNR, Fe2CNR and Fe3CNR).

Secondary Outcome Measures

Relevant Dynamic MRI (Dynamic Contrast Enhancement [DCE] and DSC) Signal Intensity Changes for Permeability and Perfusion

Mixed model repeated measures ANOVAs will be fit. Factors will include imaging agent (Gd or ferumoxytol) and field strength (3T and 7T). Each subject will contribute one measure for each combination of imaging agent and field strength (4 measures total).

Change in Cerebral Blood Volume (CBV) Measurements, Quantified Using DSC Techniques

Blood volumes will be compared using repeated measures ANOVA to compare the imaging agents.

Change in Tumor Microvascularity on Susceptibility-weighted Images (SWI) Before and After Ferumoxytol

Analysis will also include covariates of prior therapy. For the comparisons between treated and untreated subjects, means and confidence intervals will be estimated for each group for the perfusion and permeability measures and for the baseline characteristics.

Presence of Iron Staining

The pathology will be analyzed qualitatively for the presence of iron staining. The amount and localization of the staining will be assessed, with attention paid to whether the tumor cells themselves or reactive cells in and around the tumor demonstrate iron uptake.

Full Information

NCT ID

NCT00659126

First Posted

April 10, 2008

Last Updated

August 16, 2023

Sponsor

OHSU Knight Cancer Institute

Collaborators

National Cancer Institute (NCI), Oregon Health and Science University

1. Study Identification

Unique Protocol Identification Number

NCT00659126

Brief Title

Ferumoxytol- and Gadolinium-Labeled MRI in Measuring Tumors Before or After Treatment in Patients With Primary or Metastatic Brain Tumors

Official Title

A Phase II Study of Ferumoxytol and Gadolinium Magnetic Resonance Imaging at 3T and 7T in Subjects With Primary or Metastatic Brain Tumors Either Before or After Therapy

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Terminated

Why Stopped

Loss of funding

Study Start Date

November 16, 2006 (Actual)

Primary Completion Date

December 31, 2019 (Actual)

Study Completion Date

December 31, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

OHSU Knight Cancer Institute

Collaborators

National Cancer Institute (NCI), Oregon Health and Science University

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This phase II trial studies how well magnetic resonance imaging (MRI) using contrast imaging agent ferumoxytol works in comparison to standard imaging agent gadolinium in measuring tumors in patients undergoing treatment for brain tumors or other tumors that have spread to the brain. Diagnostic procedures, such as MRI, may help find and diagnose disease and find out how far the disease has spread. MRI scans use radio waves and a powerful magnet linked to a computer to create detailed pictures of areas inside the body. The contrast imaging agent ferumoxytol consists of small iron particles taken by the blood stream to the brain and to the area of the tumor. It is highly visible on the MRI, and may help visualize the blood flow going through the tumor better than gadolinium can. Using a more sensitive and faster 7 Tesla (7T) magnet MRI in conjunction with a contrast imaging agent may provide a better way to measure tumors than the 3 Tesla (3T) magnet MRI in patients with brain tumors.

Detailed Description

PRIMARY OBJECTIVES: I. To compare quantitative blood brain barrier permeability measurements (derived transfer coefficient [Ktrans]) of a standard gadolinium (Gd) MRI contrast agent at 3T and 7T using dynamic contrast enhancement (DCE) MRI. II. To compare dynamic susceptibility contrast (DSC) based perfusion measures at 3T and 7T. SECONDARY OBJECTIVES: I. To describe the blood brain barrier permeability to ferumoxytol (ferumoxytol non-stoichiometric magnetite) and to a standard gadolinium-based MRI contrast agent using signal intensity changes as described above. II. To describe cerebral blood volume (CBV) measurements obtained using a standard gadolinium MRI contrast agent and ferumoxytol. III. To evaluate tumor microvascularity on susceptibility-weighted images (SWI). IV. To describe the microscopic distribution of ferumoxytol particles in tissue removed from subjects undergoing surgery. OUTLINE: Patients are assigned to 3T or 7T magnet within the subgroups. Patients receive gadolinium intravenously (IV) on day 1 and ferumoxytol non-stoichiometric magnetite IV on day 2. Patients undergo anatomical MRI sequences with 3T or 7T at baseline and on days 1-3. Patients also undergo DSC MRI and DCE MRI on days 1-2. Day 1 and day 2 imaging sessions may be separated by up to 7 days. After completion of study, patients are followed up at approximately 4-6 weeks.

6. Conditions and Keywords

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

Metastatic Malignant Neoplasm in the Brain, Primary 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

40 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Diagnostic (Gd, ferumoxytol, 3T or 7T MRI)

Arm Type

Experimental

Arm Description

Intervention Type

Procedure

Intervention Name(s)

3 Tesla Magnetic Resonance Imaging

Other Intervention Name(s)

3 Tesla MRI, 3T MRI

Intervention Description

Undergo 3T MRI

Intervention Type

Procedure

Intervention Name(s)

Dynamic Contrast-Enhanced Magnetic Resonance Imaging

Other Intervention Name(s)

DCE MRI, DCE-MRI, DYNAMIC CONTRAST ENHANCED MRI

Intervention Description

Undergo DCE MRI

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 DSC MRI

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)

Gadolinium

Other Intervention Name(s)

Intervention Description

Given IV

Intervention Type

Procedure

Intervention Name(s)

High Field Strength Magnetic Resonance Imaging

Other Intervention Name(s)

High Field Strength MRI

Intervention Description

Undergo 7T MRI

Intervention Type

Procedure

Intervention Name(s)

Susceptibility Weighted Imaging

Other Intervention Name(s)

BOLD Venographic Imaging, BOLD Venography, SWI

Intervention Description

Undergo SWI

Primary Outcome Measure Information:

Title

Contrast to Noise Ratio (CNR), in Terms of Normalized Signal Intensity Changes, for T1-weighted MRI Signal at 3T and 7T (Gadolinium [Gd] T1-weighted Magnetic Resonance Imaging [MRI] DCE Data Only)

Description

Time Frame

Baseline to day 1

Title

CNR, in Terms of Normalized Signal Intensity Changes, for Dynamic Susceptibility Contrast (DSC) MRI Data Sets at 3T and 7T (Gadolinium and Ferumoxytol)

Description

Time Frame

Day 1 to day 2

Secondary Outcome Measure Information:

Title

Relevant Dynamic MRI (Dynamic Contrast Enhancement [DCE] and DSC) Signal Intensity Changes for Permeability and Perfusion

Description

Time Frame

Day 1 to day 2

Title

Change in Cerebral Blood Volume (CBV) Measurements, Quantified Using DSC Techniques

Description

Blood volumes will be compared using repeated measures ANOVA to compare the imaging agents.

Time Frame

Day 1 to day 2

Title

Change in Tumor Microvascularity on Susceptibility-weighted Images (SWI) Before and After Ferumoxytol

Description

Time Frame

Day 1 to day 2

Title

Presence of Iron Staining

Description

Time Frame

At time of surgery

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Subjects with radiographically suspected, histologically or cytologically confirmed primary brain tumors or brain metastasis are eligible Subjects may be enrolled at any point in diagnosis or treatment Subjects must have had radiographically evaluable or measurable disease with standard magnetic resonance (MR) imaging Members of all races and ethnic groups will be included Eastern Cooperative Oncology Group (ECOG) performance status =< 3 (Karnofsky performance status [KPS] >= 30) Ability to understand and the willingness to sign a written informed consent document, or have a representative able to consent for the subject Sexually active women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; or abstinence) prior to study treatment and for the duration of study treatment; should a female become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately Subject agrees to complete follow up visit 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 Subjects who have a contraindication for MRI: metal in their bodies (a cardiac pacemaker or other incompatible device), are severely agitated, need monitored anesthesia for scanning, or have an allergy to Gd contrast material Subjects with known hepatic insufficiency or cirrhosis History of allergic reactions attributed to compounds of similar chemical or biologic composition to ferumoxytol Subjects with known or suspected iron overload (genetic hemochromatosis or history of multiple transfusions) Subjects expecting to undergo surgery between the imaging sessions; subjects may undergo surgery at any time before the first, or after the last imaging session; this exclusion only applies to each study visit (3 day scanning session), and does not apply to the time (at least 3 weeks) between each study visit Uncontrolled concurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Pregnant or lactating women are excluded from this study Inability or unwillingness to undergo the complete series of imaging sessions; inability or unwillingness to complete the one month follow-up Human immunodeficiency virus (HIV)-positive subjects on combination antiretroviral therapy are ineligible Subjects with glomerular filtration rate (GFR) < 50 Subjects with three or more drug allergies from separate drug classes

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Edward Neuwelt

Organizational Affiliation

OHSU Knight Cancer Institute

Official's Role

Principal Investigator

Facility Information:

Facility Name

OHSU Knight Cancer Institute

City

Portland

State/Province

Oregon

ZIP/Postal Code

97239

Country

United States

12. IPD Sharing Statement

Learn more about this trial

Ferumoxytol- and Gadolinium-Labeled MRI in Measuring Tumors Before or After Treatment in Patients With Primary or Metastatic Brain Tumors

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