Gadobutrol Versus Gadopentetate Dimeglumine or Gadobenate Dimeglumine Before DCE-MRI in Diagnosing Patients With Multiple Sclerosis, Grade II-IV Glioma, or Brain Metastases

Study Overview
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Brief Summary
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This pilot clinical trial compares gadobutrol with standard of care contrast agents, gadopentetate dimeglumine or gadobenate dimeglumine, before dynamic contrast-enhanced (DCE)-magnetic resonance imaging (MRI) in diagnosing patients with multiple sclerosis, grade II-IV glioma, or tumors that have spread to the brain. Gadobutrol is a type of contrast agent that may increase DCE-MRI sensitivity for the detection of tumors or other diseases of the central nervous system. It is not yet known whether gadobutrol is more effective than standard of care contrast agents before DCE-MRI in diagnosing patients with multiple sclerosis, grade II-IV glioma, or tumors that have spread to the brain.

Detailed Description
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PRIMARY OBJECTIVES: I. To determine whether Gadavist® (gadobutrol) is consistent with Magnevist® (gadopentetate dimeglumine) or Multihance (gadobenate dimeglumine) in the preoperative grading of gliomas utilizing DCE MRI. II. To determine whether Gadavist® is consistent with Magnevist® or Multihance in identifying the number of cerebral metastases from a primary cancer elsewhere in the body using T1-weighted post contrast MRI. III. To determine if Gadavist® is consistent with Magnevist® or Multihance in identifying multiple sclerosis (MS) plaques using T1-weighted post contrast MRI. IV. To determine if Gadavist® produces similar MR perfusion/permeability values of MS lesions as Magnevist® or Multihance. V. Descriptive analysis to present the different rating patterns of Gadavist® versus Magnevist® or Multihance in differentiating therapeutic necrosis from recurrent tumor in gliomas utilizing DCE MRI. OUTLINE: Patients receive standard of care gadopentetate dimeglumine intravenously (IV) twice within 5 minutes or gadobenate dimeglumine IV twice within 5 minutes and then undergo DCE-MRI on day 1. Patients also receive gadobutrol IV twice within 5 minutes and then undergo DCE-MRI over approximately 30 minutes on day 3, 4, 5, 6, or 7. After completion of study, patients are followed up at 7 days.

Official Title
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Dynamic Contrast Enhanced Steady State T1-Weighted Perfusion MRI (DCE MRI): Characterization of Intracranial Lesions

Conditions
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Adult Anaplastic (Malignant) Meningioma, Adult Anaplastic Astrocytoma, Adult Anaplastic Ependymoma, Adult Anaplastic Oligodendroglioma, Adult Brain Stem Glioma, Adult Choroid Plexus Neoplasm, Adult Diffuse Astrocytoma, Adult Ependymoblastoma, Adult Ependymoma, Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma, Adult Grade II Meningioma, Adult Medulloblastoma, Adult Mixed Glioma, Adult Oligodendroglioma, Adult Papillary Meningioma, Adult Pineal Gland Astrocytoma, Adult Pineoblastoma, Adult Primary Melanocytic Lesion of Meninges, Adult Supratentorial Primitive Neuroectodermal Tumor, Malignant Adult Intracranial Hemangiopericytoma, Metastatic Malignant Neoplasm in the Brain, Multiple Sclerosis, Recurrent Adult Brain Neoplasm

Intervention / Treatment
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* Procedure: Dynamic Contrast-Enhanced Magnetic Resonance Imaging
* Drug: Gadobenate Dimeglumine
* Drug: Gadobutrol
* Radiation: Gadopentetate Dimeglumine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of multiple sclerosis, known or suspected diagnosis of glioma, or known or suspected diagnosis of cerebral metastasis Scheduled or to be scheduled for a follow-up MRI per standard of care for their disease Minimum permitted time intervals from prior treatments are 6 weeks for intracranial surgery Adequate renal function (serum creatinine =< 1.5 mg/dL) Subject must sign a study-specific informed consent Exclusion Criteria: Medically unstable Renal impairment (glomerular filtration rate [GFR] < 60 mL/min/1.73m^2) or history of existing nephrogenic systemic fibrosis (NSF) Cardiac pacemaker A serious concurrent infection, illness, or medical condition Subjects with any surgical clip, external clips, or any other ferromagnetic device, that is contraindicated for use in MRI Subject is claustrophobic and cannot cooperate for the MRI Females who are pregnant or nursing Any other condition that would compromise the scan with reasonable safety

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Diagnostic (Magnevist/Multihance, Gadavist, DCE-MRI)<br>Patients receive standard of care gadopentetate dimeglumine IV twice within 5 minutes or gadobenate dimeglumine IV twice within 5 minutes and then undergo DCE-MRI on day 1. Patients also receive gadobutrol IV twice within 5 minutes and then undergo DCE-MRI over approximately 30 minutes on day 3, 4, 5, 6, or 7. | Procedure: Dynamic Contrast-Enhanced Magnetic Resonance Imaging<br>* Undergo DCE-MRI<br>* Other names: DYNAMIC CONTRAST ENHANCED MRI;Drug: Gadobenate Dimeglumine<br>* Given IV<br>* Other names: MultiHance;Drug: Gadobutrol<br>* Given IV<br>* Other names: ZK 135079;Radiation: Gadopentetate Dimeglumine<br>* Given IV<br>* Other names: ZK 93035;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Agreement of using Magnevist® or Multihance versus Gadavist® on glioma grading | Weighted Kappa analysis will be used to examine the agreement of using Magnevist® or Multihance versus Gadavist® on glioma grading. | Up to 7 days |