MRI with Gadolinium + Ferumoxytol for Brain Conditions

Overseen By Lisa C Muir, MPA:HA, CCRP

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: OHSU Knight Cancer Institute

Must not be taking: Parenteral iron, Gadolinium

Disqualifiers: Uncal herniation, Pregnancy, Iron overload, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

150 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well gadolinium and ferumoxytol magnetic resonance imaging (MRI) work in diagnosing patients with abnormalities in the central nervous system. Diagnostic procedures, such as gadolinium and ferumoxytol MRI, may help find and diagnose abnormalities in the central nervous system.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you have allergies to certain drugs or have received ferumoxytol recently, you may not be eligible to participate.

What data supports the effectiveness of the drug Ferumoxytol in MRI for brain conditions?

Research shows that Ferumoxytol-enhanced MRI is as effective as gadolinium-enhanced MRI in detecting brain metastases, and it may be a safer alternative for patients who cannot use gadolinium. Ferumoxytol is biodegradable and does not stay in the brain long-term, making it a promising option for MRI imaging, especially in children. ^{1 2 3 4 5}

Is MRI with Ferumoxytol and Gadolinium safe for humans?

Research shows that using ferumoxytol as a contrast agent in MRI is generally safe, with no serious adverse events reported. Some mild to moderate reactions occurred in a small percentage of cases, but overall, it has a positive safety profile. ^{3 6 7 8 9}

How does the treatment using MRI with Gadolinium and Ferumoxytol differ from other treatments for brain conditions?

This treatment is unique because it uses ferumoxytol, an iron oxide nanoparticle, as an alternative to gadolinium for MRI contrast, which is beneficial for patients who cannot use gadolinium due to safety concerns. Ferumoxytol provides prolonged imaging signals and is not deposited in the brain, making it a safer option for certain patients, including children. ^{1 2 3 5 10}

Research Team

Michael F Regner, MD

Principal Investigator

OHSU Knight Cancer Institute

Eligibility Criteria

This trial is for individuals with brain abnormalities (tumors or other issues) who have neurological symptoms like headaches or seizures. They must be over 10 years old, able to undergo MRI without anesthesia, and not pregnant. Women of childbearing age should use contraception. Participants can't join if they have severe brain swelling signs, are pregnant/lactating, have iron overload conditions, recent ferumoxytol use, multiple drug allergies, or certain metal implants.

Inclusion Criteria

I am at least 10 years old.

All subjects, or their legal guardians, must sign a written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization in accordance with institutional guidelines

I have experienced neurological symptoms like headaches or seizures.

Exclusion Criteria

Subjects with three or more drug allergies from separate drug classes

I do not have severe brain symptoms like sudden pupil changes, quick muscle weakness, or fast drops in alertness.

I do not have genetic hemochromatosis or it has been ruled out with normal TS and SF tests.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive gadolinium and ferumoxytol intravenously and undergo MRI over 60 minutes on day 1

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Treatment Details

Interventions

• Ferumoxytol
• Gadolinium
• Magnetic Resonance Imaging

Trial Overview The study is testing how well two types of MRI contrast agents—gadolinium and ferumoxytol—work in diagnosing central nervous system problems. It aims to improve detection and diagnosis of brain-related health issues by comparing the effectiveness of these imaging techniques.

Participant Groups

Group I: Group II (ferumoxytol, gadolinium, MRI) Experimental Treatment 3 Interventions

Patients receive ferumoxytol IV and then gadolinium IV and undergo MRI over 60 minutes on day 1.

Group II: Group I (gadolinium, ferumoxytol, MRI) Experimental Treatment 3 Interventions

Patients receive gadolinium IV and then ferumoxytol IV and undergo MRI over 60 minutes on day 1.

Magnetic Resonance Imaging is already approved in United States for the following indications:

Approved in United States as Lumakras (sotorasib) for:

• Non-small cell lung cancer with KRAS G12C mutation

Approved in United States as Vectibix (panitumumab) for:

• Advanced colorectal cancer that is wild-type RAS

Who Is Running the Clinical Trial?

OHSU Knight Cancer Institute

Lead Sponsor

Trials

239

Recruited

2,089,000+

Oregon Health and Science University

Collaborator

Trials

1,024

Recruited

7,420,000+

Celgene Corporation

Industry Sponsor

Trials

446

Recruited

58,500+

Mark Alles

Celgene Corporation

Chief Executive Officer since 2016

Bachelor's degree from Lock Haven University of Pennsylvania

Sol J. Barer

Celgene Corporation

Chief Medical Officer since 2006

PhD in Organic and Physical Chemistry from Rutgers University

Findings from Research

Ferumoxytol, an iron oxide nanoparticle, provides enhanced imaging of malignant brain tumors, peaking in contrast enhancement 24 to 28 hours after injection, making it effective for dynamic MRI assessments.

Unlike gadolinium, which leaks from blood vessels early, ferumoxytol remains intravascular during the initial phase, improving the accuracy of tumor perfusion evaluations across various magnetic field strengths.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The potential of ferumoxytol nanoparticle magnetic resonance imaging, perfusion, and angiography in central nervous system malignancy: a pilot study. Neuwelt, EA., Várallyay, CG., Manninger, S., et al.[2022]

Ferumoxytol-enhanced MRI is as effective as gadolinium-enhanced MRI for detecting intracranial metastatic disease, based on a study of 19 patients with various types of cancer.

The study found no significant differences in the number or size of metastatic lesions detected by either imaging method, suggesting that ferumoxytol could be a safe alternative when gadolinium is contraindicated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ferumoxytol-Enhanced MRI Is Not Inferior to Gadolinium-Enhanced MRI in Detecting Intracranial Metastatic Disease and Metastasis Size. Hamilton, BE., Barajas, R., Nesbit, GM., et al.[2021]

Ferumoxytol, an FDA-approved iron supplement, shows promise as a safer alternative to gadolinium-based contrast agents for MRI, particularly in children, as it does not deposit in the brain and can be metabolized.

Studies indicate that ferumoxytol provides significant signal enhancement in MRI, making it a potentially effective option for improving diagnostic accuracy in pediatric imaging compared to traditional gadolinium chelates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How to stop using gadolinium chelates for magnetic resonance imaging: clinical-translational experiences with ferumoxytol. Daldrup-Link, HE., Theruvath, AJ., Rashidi, A., et al.[2022]

Ferumoxytol, an iron oxide nanoparticle approved for treating iron deficiency, is being increasingly used off-label as an MRI contrast agent, especially in pediatric patients, due to its safety profile and lack of long-term tissue retention.

Unlike traditional gadolinium-based contrast agents, ferumoxytol is biodegradable and poses no risk of nephrogenic systemic fibrosis, making it a safer alternative for high-quality vascular and cancer imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ferumoxytol-Enhanced MRI in Children and Young Adults: State of the Art. Adams, LC., Jayapal, P., Ramasamy, SK., et al.[2023]

In a study of 49 MRI scans from 70 adults, ferumoxytol was found to provide different enhancement characteristics compared to gadoteridol, particularly in T1-weighted images, suggesting its potential as an alternative MRI contrast agent for patients with renal failure.

Ferumoxytol showed contrast-enhanced hypointensity in 53% of cases, while gadoteridol showed none, indicating that ferumoxytol may have unique diagnostic properties that warrant further investigation across various CNS disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative analysis of ferumoxytol and gadoteridol enhancement using T1- and T2-weighted MRI in neuroimaging. Hamilton, BE., Nesbit, GM., Dosa, E., et al.[2021]

In a study involving 49 pediatric patients and 19 young adults, ferumoxytol was found to be well tolerated as an intravenous MRI contrast agent, with only four mild adverse events reported, all of which were self-resolving.

No significant effects on vital signs, kidney function, or liver enzymes were observed after administration, indicating a favorable safety profile for doses of 5 mg Fe/kg or lower, although further research is needed to assess the risk of anaphylactic reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Report of Ferumoxytol for Magnetic Resonance Imaging in Children and Young Adults. Muehe, AM., Feng, D., von Eyben, R., et al.[2018]

In a multicenter study involving 3215 patients who received 4240 ferumoxytol injections for MRI, the use of ferumoxytol was well tolerated with no severe or life-threatening adverse events reported.

Only 1.9% of patients experienced adverse reactions related to ferumoxytol, mostly mild, indicating a positive safety profile for its off-label diagnostic use as an alternative to gadolinium-based contrast agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter Safety and Practice for Off-Label Diagnostic Use of Ferumoxytol in MRI. Nguyen, KL., Yoshida, T., Kathuria-Prakash, N., et al.[2023]

Ferumoxytol shows strong relaxation properties, making it a promising alternative to gadolinium-based contrast agents for magnetic resonance imaging (MRI), with effective relaxivities measured at both 1.5 T and 3.0 T.

The study highlights that while ferumoxytol's relaxation rates are linear in saline and plasma, they exhibit nonlinear behavior in blood, which is crucial for optimizing MRI protocols using this agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relaxivity of Ferumoxytol at 1.5 T and 3.0 T. Knobloch, G., Colgan, T., Wiens, CN., et al.[2020]

In a study of 86 pediatric patients and young adults, ferumoxytol was found to be an effective intravenous MRI contrast agent, with 95.4% of the images rated as at least diagnostic quality by radiologists.

While there was a statistically significant but clinically insignificant drop in blood pressure after ferumoxytol injection, further large-scale studies are needed to determine optimal dosing and safety monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemodynamic safety and efficacy of ferumoxytol as an intravenous contrast agents in pediatric patients and young adults. Ning, P., Zucker, EJ., Wong, P., et al.[2016]

Gadolinium-based contrast agents, while commonly used in MRI, raise safety concerns due to risks like nephrogenic systemic fibrosis and tissue deposition, particularly in certain patient populations.

Ferumoxytol presents a promising alternative as a contrast medium for MRI, offering unique properties such as prolonged intravascular signal and delayed uptake by macrophages, which could enhance its clinical applications in abdominal imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pictorial review on abdominal applications of ferumoxytol in MR imaging. Kordbacheh, H., Baliyan, V., Parakh, A., et al.[2020]

References

1. United States pubmed.ncbi.nlm.nih.gov

The potential of ferumoxytol nanoparticle magnetic resonance imaging, perfusion, and angiography in central nervous system malignancy: a pilot study. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Ferumoxytol-Enhanced MRI Is Not Inferior to Gadolinium-Enhanced MRI in Detecting Intracranial Metastatic Disease and Metastasis Size. [2021]

3. Germany pubmed.ncbi.nlm.nih.gov

How to stop using gadolinium chelates for magnetic resonance imaging: clinical-translational experiences with ferumoxytol. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Ferumoxytol-Enhanced MRI in Children and Young Adults: State of the Art. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Comparative analysis of ferumoxytol and gadoteridol enhancement using T1- and T2-weighted MRI in neuroimaging. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Safety Report of Ferumoxytol for Magnetic Resonance Imaging in Children and Young Adults. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Multicenter Safety and Practice for Off-Label Diagnostic Use of Ferumoxytol in MRI. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Relaxivity of Ferumoxytol at 1.5 T and 3.0 T. [2020]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Hemodynamic safety and efficacy of ferumoxytol as an intravenous contrast agents in pediatric patients and young adults. [2016]

10. United States pubmed.ncbi.nlm.nih.gov

Pictorial review on abdominal applications of ferumoxytol in MR imaging. [2020]