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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
  Purpose
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 Intervention 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

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by OHSU Knight Cancer Institute:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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).


Estimated Enrollment: 150
Study Start Date: November 2006
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00659126

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

Responsible Party: OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier: NCT00659126     History of Changes
Other Study ID Numbers: IRB00002864  NCI-2015-00225  SOL-06077-L  IRB00002864  P30CA069533 
Study First Received: April 10, 2008
Last Updated: June 8, 2016
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on September 27, 2016