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

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Metastatic Malignant Neoplasm in the Brain; Primary Brain Neoplasm	Procedure: 3 Tesla Magnetic Resonance Imaging; Procedure: Dynamic Contrast-Enhanced Magnetic Resonance Imaging; Procedure: Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging; Drug: Ferumoxytol; Drug: Gadolinium; Procedure: High Field Strength Magnetic Resonance Imaging; Procedure: Susceptibility Weighted Imaging	Phase 2

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	150 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Diagnostic
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 Start Date :	November 2006
Estimated Primary Completion Date :	December 2018
Estimated Study Completion Date :	December 2019

Arms and Interventions

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Arm

Intervention/treatment

Experimental: Diagnostic (Gd, ferumoxytol, 3T or 7T MRI); 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.

Procedure: 3 Tesla Magnetic Resonance Imaging; Undergo 3T MRI; Other Names: 3 Tesla MRI; 3T MRI Procedure: Dynamic Contrast-Enhanced Magnetic Resonance Imaging; Undergo DCE MRI; Other Names: DCE MRI; DCE-MRI; DYNAMIC CONTRAST ENHANCED MRI Procedure: Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging; Undergo DSC MRI; Other Name: Dynamic Susceptibility Contrast-Enhanced MRI Drug: Ferumoxytol; Given IV; Other Names: Feraheme; FERUMOXYTOL NON-STOICHIOMETRIC MAGNETITE Drug: Gadolinium; Given IV; Other Name: Gd Procedure: High Field Strength Magnetic Resonance Imaging; Undergo 7T MRI; Other Name: High Field Strength MRI Procedure: Susceptibility Weighted Imaging; Undergo SWI; Other Names: BOLD Venographic Imaging; BOLD Venography; SWI

Outcome Measures

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Primary Outcome Measures :

1. CNR, in terms of normalized signal intensity changes, for DSC MRI data sets at 3T and 7T (ferumoxytol only) [ Time Frame: Day 2 to day 3 ]
   Paired sample t-tests will be used for primary descriptive comparisons. Secondary analyses will use a repeated measures 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.
2. CNR, in terms of normalized signal intensity changes, for T1-weighted MRI signal at 3T and 7T (Gd T1-weighted MRI data only) [ Time Frame: Baseline to day 1 ]
   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.

Secondary Outcome Measures :

1. Change in CBV measurements, quantified using DSC techniques [ Time Frame: Day 1 to day 2 ]
   Blood volumes will be compared using repeated measures ANOVA to compare the imaging agents.
2. Change in tumor microvascularity on SWI before and after ferumoxytol [ Time Frame: Day 2 to day 3 ]
   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.
3. Presence of iron staining [ Time Frame: At time of surgery ]
   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.
4. Relevant dynamic MRI (DCE and DSC) signal intensity changes for permeability and perfusion [ Time Frame: Day 1 to day 2 ]
   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).

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Subjects with radiographically suspected, histologically or cytologically confirmed primary brain tumors or brain metastasis are eligible
• Subjects may have any extent of disease
• Subjects must have had radiographically evaluable or measurable disease with standard magnetic resonance (MR) imaging
• Subjects may or may not have had prior surgery, radiation therapy, or chemotherapy
• 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

Contacts and Locations

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Locations

United States, Oregon
OHSU Knight Cancer Institute	Recruiting
Portland, Oregon, United States, 97239
Contact: Edward A. Neuwelt 503-494-5626 neuwelte@ohsu.edu
Principal Investigator: Edward A. Neuwelt

Sponsors and Collaborators

OHSU Knight Cancer Institute

National Cancer Institute (NCI)

Investigators

Principal Investigator:	Edward Neuwelt	OHSU Knight Cancer Institute

More Information

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Responsible Party:	Edward Neuwelt, Professor, OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier:	NCT00659126 History of Changes
Other Study ID Numbers:	IRB00002864; NCI-2015-00225 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); SOL-06077-L; IRB00002864 ( Other Identifier: OHSU Knight Cancer Institute ); P30CA069533 ( U.S. NIH Grant/Contract )
First Posted:	April 16, 2008
Last Update Posted:	April 21, 2017
Last Verified:	April 2017

Additional relevant MeSH terms:

Neoplasms; Brain Neoplasms; Neoplasms, Second Primary; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases	Central Nervous System Diseases; Nervous System Diseases; Ferrosoferric Oxide; Hematinics; Parenteral Nutrition Solutions; Pharmaceutical Solutions