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

NCT00659126 | Terminated Phase 2 Results DMC

• 4 other identifiers: IRB00002864NCI-2015-00225SOL-06077-LR01CA137488
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Metastatic Malignant Neoplasm in the Brain; Primary Brain Neoplasm

Outcome Measures

Primary Outcomes (2)

• Contrast to Noise Ratio (CNR), in Terms of Normalized Signal Intensity Changes, for T1-weighted MRI Signal at 3T and 7T (Gadolinium [Gd] T1-weighted Magnetic Resonance Imaging [MRI] DCE Data Only)

  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.

  Baseline to day 1

• CNR, in Terms of Normalized Signal Intensity Changes, for Dynamic Susceptibility Contrast (DSC) MRI Data Sets at 3T and 7T (Gadolinium and Ferumoxytol)

  A two sample t-test was used for primary descriptive comparisons since CNR was measured on different subjects at 3T and 7T. There were no repeated measures in the resulting data. Given the small sample size, a linear regression was conducted to compare CNR between 3T and 7T only adjusted for Fe dose. No other adjusted analyses were conducted. CNR was compared between 3T and 7T for both Ferumoxytol and Gadolinum. Ferumoxytol was administered using three injections and CNR was measured after each injection, thus we have three measures of CNR (Fe1CNR, Fe2CNR and Fe3CNR).

  Day 1 to day 2

Secondary Outcomes (4)

• Relevant Dynamic MRI (Dynamic Contrast Enhancement [DCE] and DSC) Signal Intensity Changes for Permeability and Perfusion

  Day 1 to day 2

• Change in Cerebral Blood Volume (CBV) Measurements, Quantified Using DSC Techniques

  Day 1 to day 2

• Change in Tumor Microvascularity on Susceptibility-weighted Images (SWI) Before and After Ferumoxytol

  Day 1 to day 2

• Presence of Iron Staining

  At time of surgery

Study Arms (1)

Diagnostic (Gd, ferumoxytol, 3T or 7T MRI)

EXPERIMENTAL

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; 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

Interventions

3 Tesla Magnetic Resonance Imaging PROCEDURE

Undergo 3T MRI

Also known as: 3 Tesla MRI, 3T MRI

Diagnostic (Gd, ferumoxytol, 3T or 7T MRI)

Dynamic Contrast-Enhanced Magnetic Resonance Imaging PROCEDURE

Undergo DCE MRI

Also known as: DCE MRI, DCE-MRI, DYNAMIC CONTRAST ENHANCED MRI

Diagnostic (Gd, ferumoxytol, 3T or 7T MRI)

Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging PROCEDURE

Undergo DSC MRI

Also known as: DSC-MRI, Dynamic Susceptibility Contrast-Enhanced MRI, DYNAMIC SUSCEPTIBILITY-CONTRAST MRI

Diagnostic (Gd, ferumoxytol, 3T or 7T MRI)

Ferumoxytol DRUG

Given IV

Also known as: Feraheme, Ferumoxytol Non-Stoichiometric Magnetite

Diagnostic (Gd, ferumoxytol, 3T or 7T MRI)

Gadolinium DRUG

Given IV

Also known as: Gd

Diagnostic (Gd, ferumoxytol, 3T or 7T MRI)

High Field Strength Magnetic Resonance Imaging PROCEDURE

Undergo 7T MRI

Also known as: High Field Strength MRI

Diagnostic (Gd, ferumoxytol, 3T or 7T MRI)

Susceptibility Weighted Imaging PROCEDURE

Undergo SWI

Also known as: BOLD Venographic Imaging, BOLD Venography, SWI

Diagnostic (Gd, ferumoxytol, 3T or 7T MRI)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects with radiographically suspected, histologically or cytologically confirmed primary brain tumors or brain metastasis are eligible
• Subjects may be enrolled at any point in diagnosis or treatment
• Subjects must have had radiographically evaluable or measurable disease with standard magnetic resonance (MR) imaging
• Members of all races and ethnic groups will be included
• 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

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead
• National Cancer Institute (NCI): collaborator
• Oregon Health and Science University: collaborator

Study Sites (1)

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

MeSH Terms

Conditions

Brain Neoplasms

Interventions

Ferrosoferric Oxide; Gadolinium

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Ferric Compounds; Iron Compounds; Inorganic Chemicals; Ferrous Compounds; Minerals; Lanthanoid Series Elements; Metals, Rare Earth; Elements; Metals

Results Point of Contact

• Title: Amy Huddleston
• Organization: Oregon Health and Science University

huddlesa@ohsu.edu

5034945626

Study Officials

• Edward Neuwelt

  OHSU Knight Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 10, 2008
• First Posted: April 16, 2008
• Study Start: November 16, 2006
• Primary Completion: December 31, 2019
• Study Completion: December 31, 2020
• Last Updated: September 7, 2023
• Results First Posted: September 7, 2023

Record last verified: 2023-08

Locations

US (1)