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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2016 by OHSU Knight Cancer Institute
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier:
NCT00659126
First received: April 10, 2008
Last updated: June 8, 2016
Last verified: June 2016

April 10, 2008
June 8, 2016
November 2006
December 2018   (final data collection date for primary outcome measure)
  • 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 ] [ Designated as safety issue: No ]
    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.
  • 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 ] [ Designated as safety issue: No ]
    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.
The primary objective of this project is to compare quantitative imaging measures of brain tumor vascularity obtained from 3 T and 7T MRI instruments [ Time Frame: 3 days ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00659126 on ClinicalTrials.gov Archive Site
  • Change in CBV measurements, quantified using DSC techniques [ Time Frame: Day 1 to day 2 ] [ Designated as safety issue: No ]
    Blood volumes will be compared using repeated measures ANOVA to compare the imaging agents.
  • Change in tumor microvascularity on SWI before and after ferumoxytol [ Time Frame: Day 2 to day 3 ] [ Designated as safety issue: No ]
    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 [ Time Frame: At time of surgery ] [ Designated as safety issue: No ]
    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.
  • Relevant dynamic MRI (DCE and DSC) signal intensity changes for permeability and perfusion [ Time Frame: Day 1 to day 2 ] [ Designated as safety issue: No ]
    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).
  • To compare blood brain barrier permeabilities of Ferumoxytol and a standard gadolinium based MRI contrast agent. [ Time Frame: 3 days ] [ Designated as safety issue: No ]
  • To compare cerebral blood volume (CBV) measurements obtained using a standard gadolinium MRI contrast agent and ferumoxytol CBV will be quantified using dynamic susceptibility contrast (DSC) techniques using both Gd and Ferumoxytol contrast agents. [ Time Frame: 3 days ] [ Designated as safety issue: No ]
  • To compare perfusion and permeability parameters between treated and untreated patients [ Time Frame: 3 days ] [ Designated as safety issue: No ]
  • To determine the microscopic distribution of ferumoxytol particles in tissue removed from patients undergoing surgery. . [ Time Frame: 3 days ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Ferumoxytol- and Gadolinium-Labeled MRI in Measuring Tumors Before or After Treatment in Patients With Primary or Metastatic Brain Tumors
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
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.

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.

Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
  • Metastatic Malignant Neoplasm in the Brain
  • Primary Brain Neoplasm
  • 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
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.
Interventions:
  • 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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
150
December 2019
December 2018   (final data collection date for primary outcome measure)

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
Both
18 Years and older   (Adult, Senior)
No
United States
 
NCT00659126
IRB00002864, NCI-2015-00225, SOL-06077-L, IRB00002864, P30CA069533
Yes
Not Provided
Not Provided
OHSU Knight Cancer Institute
OHSU Knight Cancer Institute
National Cancer Institute (NCI)
Principal Investigator: Edward Neuwelt OHSU Knight Cancer Institute
OHSU Knight Cancer Institute
June 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP