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Gadolinium and Ferumoxytol MRI in Diagnosing Patients With Abnormalities in the Central Nervous System

Phase 2
Recruiting
Conditions
Cranial Nerve Disorder
Central Nervous System Neoplasm
Metastatic Malignant Neoplasm in the Brain
Interventions
Procedure: Magnetic Resonance Imaging
Registration Number
NCT03270059
Lead Sponsor
OHSU Knight Cancer Institute
Brief Summary

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.

Detailed Description

PRIMARY OBJECTIVES:

I. To test if prior gadolinium administration affects vascular imaging using ferumoxytol.

II. To test signal changes of T2\*w multi-echo fast field echo (mFFE) scans before and after contrast agent injection.

SECONDARY OBJECTIVES:

I. To test if ferumoxytol affects gadolinium enhanced MRI. II. To test if steady state cerebral blood volume (CBV) maps are different at various magnetic field strengths.

EXPLORATORY OBJECTIVES:

I. To explore late ferumoxytol enhancement (optional MRI) hours to days after ferumoxytol administration in various brain pathologies.

II. To evaluate the effects of ferumoxytol on malignant and non-malignant lesions in head \& neck, and liver lesions

OUTLINE: Patients are randomized into 1 of 2 groups.

GROUP I: Patients receive gadolinium intravenously (IV) and then ferumoxytol IV and undergo MRI over 60 minutes on day 1.

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

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
150
Inclusion Criteria
  • Subjects must have one of the following:

    • Neurological findings (i.e. headache, loss of consciousness, paresis, cranial neuropathy, seizures, etc.)
    • Radiological abnormalities in the brain (neoplastic or non-neoplastic in nature)
    • Neoplastic process elsewhere in the body that may affect the brain (i.e. possible metastasis, vascular compromise, treatment related changes, etc.)
  • Subjects must be able to undergo MRI imaging without anesthesia

  • Subjects must be at least 10 years of age

  • 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

  • Sexually active women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; surgical intervention i.e. tubal ligation or vasectomy; post-menopausal < 6 months; or abstinence) for at least two months after each cycle of the study; should a female become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

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, 2009); 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 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 containing contrast material
  • Subjects with known iron overload (genetic hemochromatosis); in subjects with a family history of hemochromatosis, hemochromatosis must be ruled out prior to study entry with normal values of the following blood tests: transferrin saturation (TS) test and serum ferritin (SF) test; all associated costs will be paid by the study
  • Subject who have received ferumoxytol within 3 weeks of study entry
  • Subjects with three or more drug allergies from separate drug classes

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Group II (ferumoxytol, gadolinium, MRI)GadoliniumPatients receive ferumoxytol IV and then gadolinium IV and undergo MRI over 60 minutes on day 1.
Group I (gadolinium, ferumoxytol, MRI)Magnetic Resonance ImagingPatients receive gadolinium IV and then ferumoxytol IV and undergo MRI over 60 minutes on day 1.
Group II (ferumoxytol, gadolinium, MRI)Magnetic Resonance ImagingPatients receive ferumoxytol IV and then gadolinium IV and undergo MRI over 60 minutes on day 1.
Group I (gadolinium, ferumoxytol, MRI)FerumoxytolPatients receive gadolinium IV and then ferumoxytol IV and undergo MRI over 60 minutes on day 1.
Group I (gadolinium, ferumoxytol, MRI)GadoliniumPatients receive gadolinium IV and then ferumoxytol IV and undergo MRI over 60 minutes on day 1.
Group II (ferumoxytol, gadolinium, MRI)FerumoxytolPatients receive ferumoxytol IV and then gadolinium IV and undergo MRI over 60 minutes on day 1.
Primary Outcome Measures
NameTimeMethod
Visualization of normal vasculatureUp to 5 years

Primary analysis will use the average score of the two readers. The mean difference and the associated 95% confidence interval (CI) between the two groups will be estimated using a linear regression model. Equivalence will be claimed if the 95% CI does not include 0.4 on either side (equivalence margin is 0.4).

Visualization of normal anatomical structuresUp to 5 years

Primary analysis will use the average score of the two readers. The mean difference and the associated 95% CI between the two groups will be estimated using a linear regression model. Equivalence will be claimed if the 95% CI does not include 0.4 on either side (equivalence margin is 0.4).

Visualization of abnormal vasculatureUp to 5 years

Primary analysis will use the average score of the two readers. The mean difference and the associated 95% CI between the two groups will be estimated using a linear regression model. Equivalence will be claimed if the 95% CI does not include 0.4 on either side (equivalence margin is 0.4).

Identification of the lesion corresponding areas on cerebral blood volume (CBV) mapsUp to 5 years

Will assess the confidence in identifying the lesion corresponding areas on CBV maps as well as signal change (deltaR2\*) and relative cerebral blood volume. Primary analysis will use the average score of the two readers. The mean difference and the associated 95% CI between the two groups will be estimated using a linear regression model. Equivalence will be claimed if the 95% CI does not include 0.4 on either side (equivalence margin is 0.4).

Secondary Outcome Measures
NameTimeMethod
Contrast enhancementUp to 5 years

The mean difference and the associated 95% CI before versus after ferumoxytol in the three visualization variables will be estimated using a paired t-test based on the average score of the two readers. Will use the same equivalence margin of 0.4. To compare the two magnetic field strengths, will also use a linear regression model to analyze contrast to noise ratios, Image homogeneity and susceptibility artifacts (the latter two based on average score of the two readers).

Border delineationUp to 5 years

The mean difference and the associated 95% CI before versus after ferumoxytol in the three visualization variables will be estimated using a paired t-test based on the average score of the two readers. Will use the same equivalence margin of 0.4. To compare the two magnetic field strengths, will also use a linear regression model to analyze contrast to noise ratios, Image homogeneity and susceptibility artifacts (the latter two based on average score of the two readers).

Internal morphologyUp to 5 years

The mean difference and the associated 95% CI before versus after ferumoxytol in the three visualization variables will be estimated using a paired t-test based on the average score of the two readers. Will use the same equivalence margin of 0.4. To compare the two magnetic field strengths, will also use a linear regression model to analyze contrast to noise ratios, Image homogeneity and susceptibility artifacts (the latter two based on average score of the two readers).

Trial Locations

Locations (1)

OHSU Knight Cancer Institute

🇺🇸

Portland, Oregon, United States

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