Ferumoxytol in Improving MR Imaging in Patients With High-Grade Brain Tumors or Cerebral Metastases

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2016 by OHSU Knight Cancer Institute
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier:
NCT00103038
First received: February 7, 2005
Last updated: March 25, 2016
Last verified: March 2016
  Purpose
This clinical trial studies magnetic resonance imaging (MRI) using a contrast imaging agent ferumoxytol (ferumoxytol non-stoichiometric magnetite) in improving viewing tumors in patients with high-grade brain tumors or cancer that has spread to the brain. Diagnostic procedures, such as MRI, may help find and diagnose brain tumors and find out how far the disease has spread. The contrast imaging agent ferumoxytol non-stoichiometric magnetite consists of small iron particles taken by the blood stream to the brain and to the area of the tumor. It may help visualize the blood flow going through the tumor better than the standard substance gadolinium-based contrast agent.

Condition Intervention
Central Nervous System Lymphoma
Malignant Glioma
Metastatic Malignant Neoplasm in the Brain
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: MRI-Based Angiogram

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: NCI-Sponsored Multi-Disciplinary Study for MR Imaging of Intravenous Superparamagnetic Crystalline Particle Ferumoxytol in Primary High-Grade Brain Tumors and/or Cerebral Metastases

Resource links provided by NLM:


Further study details as provided by OHSU Knight Cancer Institute:

Primary Outcome Measures:
  • Ktrans [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Appropriate descriptive statistics (mean, standard deviation, minimum, median, and maximum) will be estimated for the imaging parameters Ktrans. Frequency distributions of each parameter will also be described to assess normality. Pearson's correlation coefficients will be estimated to describe potential relationships among these various measures.

  • rCBV [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Appropriate descriptive statistics (mean, standard deviation, minimum, median, and maximum) will be estimated for the imaging parameters rCBV. Frequency distributions of each parameter will also be described to assess normality. Pearson's correlation coefficients will be estimated to describe potential relationships among these various measures.


Secondary Outcome Measures:
  • Overall survival [ Time Frame: Up to 4-6 weeks after completion of study ] [ Designated as safety issue: No ]
    To evaluate the value of rCBV for improved clinical management, overall survival times will be assessed using Kaplan-Meier product limit estimates and will compare patients with rCBV =< 1.75 and those with rCBV > 1.75 using the log-rank test. In addition, the Cox proportional hazard model will be used to estimate hazard ratios while adjusting for potential confounding variables if necessary. This analysis will be conducted for subjects of high-grade brain tumors, and other subjects separately.


Estimated Enrollment: 150
Study Start Date: February 2004
Estimated Study Completion Date: April 2020
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Diagnostic (ferumoxytol, gadolinium, DCE-MRI, DSC-MRI)
Patients receive ferumoxytol non-stoichiometric magnetite IV beginning approximately 15 seconds after start of 3T DSC-MRI and GBCA IV approximately 1 minute and 50 seconds after start of 3T DCE-MRI on day 1. Patients also undergo MRI without contrast at baseline and on day 2. Imaging with ferumoxytol, GBCA and without contrast repeats every 3 weeks for a total of 6 more imaging sessions over up to 5 years.
Procedure: 3 Tesla Magnetic Resonance Imaging
Undergo 3T MRI
Other Names:
  • 3 Tesla MRI
  • 3T MRI
Procedure: Dynamic Contrast-Enhanced Magnetic Resonance Imaging
Undergo 3T DCE-MRI
Other Names:
  • DCE MRI
  • DCE-MRI
  • DYNAMIC CONTRAST ENHANCED MRI
Procedure: Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging
Undergo 3T 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: MRI-Based Angiogram
Undergo MRA
Other Names:
  • Magnetic Resonance Angiogram
  • MRA

Detailed Description:

PRIMARY OBJECTIVES:

I. Investigate the utility of ferumoxytol and gadolinium-based contrast agent (GBCA) for improved imaging biomarkers of malignant brain tumors in a single imaging session by comparing dynamic susceptibility contrast (DSC) determined relative cerebral blood volume (rCBV) and dynamic contrast enhancement (DCE) determined vascular permeability (derived transfer coefficient [Ktrans]).

SECONDARY OBJECTIVES:

I. Compare and evaluate magnetic resonance angiography (MRA) with ferumoxytol between different time points.

II. Assess number and size of tumors imaged. III. Assess tumor vascularity. IV. Assess histology and electron microscopy (EM) on tissue samples. V. Assess differences in subjects with prior therapy versus (vs.) no prior therapy (radiation and/or chemotherapy).

VI. Assess the long term imaging characteristics of different tumors using DSC and DCE.

OUTLINE:

Patients receive ferumoxytol non-stoichiometric magnetite intravenously (IV) beginning approximately 15 seconds after start of 3T DSC-MRI and GBCA IV approximately 1 minute and 50 seconds after start of 3T DCE-MRI on day 1. Patients also undergo MRI without contrast at baseline and on day 2. Imaging with ferumoxytol, GBCA, and without contrast repeats every 3 weeks for a total of 6 more imaging sessions over up to 5 years.

After completion of study, patients are followed up at approximately 4-6 weeks.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subject must have either radiological or established histological diagnosis of the following general categories:

    • High-grade glioma/central nervous system (CNS) lymphoma or
    • Brain metastases
  • Previously untreated subjects must have a lesion on an imaging study
  • Post treatment subjects will have radiographic abnormalities that may or may not be recurrent tumor
  • Subjects agree to be contacted 4-6 weeks after each study visit
  • Subjects, or their legal guardian, 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; 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
  • Pre-imaging radiological scans/studies must be performed approximately 16 weeks prior to study entry; but not less than 24 hours prior

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 (Ferumoxytol Investigator's Drug Brochure, 2012); 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 require monitored anesthesia for MRI scanning
  • Subjects with renal insufficiency; glomerular filtration rate (GFR) < 50
  • Subjects who have a contraindication for MRI: metal in their bodies (a cardiac pacemaker or other incompatible device), are severely agitated, or have an allergy to gadolinium (Gd) contrast material
  • Subjects with known hepatic insufficiency or cirrhosis
  • Human immunodeficiency virus (HIV)-positive subjects on combination antiretroviral therapy are ineligible
  • Subjects with known or suspected iron overload (genetic hemochromatosis or history of multiple transfusions)
  • 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: NCT00103038

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: NCT00103038     History of Changes
Obsolete Identifiers: NCT00980720
Other Study ID Numbers: IRB00000813  NCI-2015-00226  ONC-03095-LX  IRB00000813  P30CA069533  R01CA137488 
Study First Received: February 7, 2005
Last Updated: March 25, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Brain Neoplasms
Neoplasms
Neoplasms, Second Primary
Brain Diseases
Central Nervous System Diseases
Central Nervous System Neoplasms
Neoplasms by Site
Nervous System Diseases
Nervous System Neoplasms
Contrast Media
Ferrosoferric Oxide
Diagnostic Uses of Chemicals
Hematinics
Hematologic Agents
Parenteral Nutrition Solutions
Pharmaceutical Solutions
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on April 27, 2016