Clinical trial NCT00103038: Ferumoxytol in Improving MR Imaging in Patients With High-Grade Brain Tumors or Cerebral Metastases
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Central Nervous System Lymphoma
Malignant Glioma
Metastatic Malignant Neoplasm in the Brain
Lead sponsor: OHSU Knight Cancer Institute
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-02-08
Enrollment: 155
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: 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.

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 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

Primary outcomes:
measure: Utility of Femumoxytol and Gadolinium Based Contrast Agents for Improved Imaging Biomarkers of Malignant Brain Tumors in a Single Session by Comparing Dynamic Contrast Enhanced Determined Vascular Permeability (Ktrans)
timeFrame: Assessed after each visit for up to 6 imaging sessions (up to 5 years)
measure: Utility of Ferumoxytol and Gadolinium Based Contrast Agents 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) Maps.
timeFrame: Summarized after completion of up to 6 imaging sessions (up to 5 years)
Secondary outcomes:
measure: Compare Number and Size of Tumors Imaged With Ferumoxytol and Gadolinium Based Contrast Agents (Cube Root Volume)
timeFrame: Summarized after completion of up to 6 imaging sessions (up to 5 years)
measure: Compare Number and Size of Tumors Imaged With Ferumoxytol and Gadolinium Based Contrast Agents (Signal Intensity)
timeFrame: Summarized after completion of up to 6 imaging sessions (up to 5 years)
measure: Overall Survival in Participants With Pseudoprogression With or Real Tumor Progression Using Ferumoxytol Enchanced Perfusion MRI
timeFrame: Assessed after each visit for up to 6 imaging sessions (up to 5 years)
Other outcomes:
Locations:
city: Portland
country: United States
facility: OHSU Knight Cancer Institute
state: Oregon
Study officials:
affiliation: OHSU Knight Cancer Institute
name: Edward Neuwelt
role: PRINCIPAL_INVESTIGATOR
References: