DSC-MRI With Ferumoxytol and DCE-MRI With Gadolinium in Imaging Vascular Properties in Younger Patients With Brain Tumors

• ClinicalTrials.gov Identifier: NCT00978562
• Recruitment Status: Unknown
• First Posted: September 17, 2009
• Results First Posted: May 23, 2017
• Last Update Posted: February 1, 2018
• Sponsor: OHSU Knight Cancer Institute
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Edward Neuwelt, OHSU Knight Cancer Institute

Study Description

Brief Summary:

This clinical trial studies dynamic susceptibility-weighted contrast enhanced magnetic resonance imaging (DSC-MRI) after administration of ferumoxytol and dynamic contrast-enhanced MRI (DCE-MRI) after administration of a gadolinium-based contrast agent (GBCA) in viewing the vessels of the brain in younger patients with brain tumors. Ferumoxytol is an experimental form of very small iron particles that are taken by the blood stream to cells adjacent and inside the tumor. These iron particles may make it easier to see the areas of the brain that are affected by tumor. Ferumoxytol may work better than standard GBCA in viewing the vessels of the brain and brain tumor on MRI. Using ferumoxytol and GBCA in the same MRI session may provide more information about tumor blood supply and the extent of the tumor.

Condition or disease	Intervention/treatment	Phase
Childhood Brain Neoplasm; Recurrent Childhood Brain Neoplasm	Procedure: Dynamic Contrast-Enhanced Magnetic Resonance Imaging; Procedure: Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging; Drug: Ferumoxytol Non-Stoichiometric Magnetite; Drug: Gadolinium	Not Applicable

Detailed Description:

PRIMARY OBJECTIVES:

I. To describe the vascular properties of pediatric brain tumors using ferumoxytol for DSC-MRI and GBCA for DCE-MRI in pediatric brain tumor (proven or presumptive) patients in a single MRI session.

II. To describe evolving imaging characteristics of tumor vasculature using DSC-MRI with ferumoxytol and DCE-MRI with GBCA in pediatric brain tumor patients.

SECONDARY OBJECTIVES:

I. Compare and evaluate magnetic resonance angiogram (MRA) with ferumoxytol between different time points.

II. To describe number and size of tumors imaged. III. To assess histology and electron microscopy (EM) on tissue samples. IV. To demonstrate differences in patients with prior therapy versus (vs.) no prior therapy (radiation and/or chemotherapy).

OUTLINE:

Patients receive ferumoxytol and gadolinium intravenously (IV) and then undergo DSC-MRI and DCE-MRI. An optional MRI without injection of a contrast agent may be obtained after 20-24 hours at the discretion of the clinician. Patients may receive up to 3 more scans at least 3 weeks apart over up to 2 years.

After completion of study treatment, patients are followed up at approximately 4-6 weeks.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 7 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Imaging Vascular Properties of Pediatric Brain Tumors Using DSC-MRI With Ferumoxytol (Code 7228) and DCE-MRI With Gadolinium in a Single Imaging Session: An NCI Sponsored Exploratory Trial
• Study Start Date: August 2009
• Actual Primary Completion Date: December 2015
• Estimated Study Completion Date: December 2018

Arms and Interventions

Arm

Intervention/treatment

Experimental: Diagnostic (DSC-MRI with ferumoxytol, DCE-MRI with gadolinium); Patients receive ferumoxytol and gadolinium IV and then undergo DSC-MRI and DCE-MRI. An optional MRI without injection of a contrast agent may be obtained after 20-24 hours at the discretion of the clinician. Patients may receive up to 3 more scans at least 3 weeks apart over up to 2 years.

Procedure: Dynamic Contrast-Enhanced Magnetic Resonance Imaging; Undergo DCE-MRI; Other Names: DCE MRI; DCE-MRI; DYNAMIC CONTRAST ENHANCED MRI; Procedure: Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging; Undergo DSC-MRI; Other Name: Dynamic Susceptibility Contrast-Enhanced MRI; Drug: Ferumoxytol Non-Stoichiometric Magnetite; Given IV; Other Names: Feraheme; Ferumoxytol; Drug: Gadolinium; Given IV; Other Name: Gd

Outcome Measures

Primary Outcome Measures :

1. Vascular Properties of Pediatric Brain Tumors Using Dynamic Susceptibility-weighted Contrast Enhanced MRI (DSC-MRI) After Administration of Ferumoxytol [ Time Frame: Up to 2 years ]
   Signal intensity, relative cerebral blood volume (rCBV) was measured. Relative CBV measurements were calculated from regions of interest (ROI) that were placed in regions of highest perfusion seen on the rCBV color overlay parametric maps.The mean of 3 regions of contralateral white matter was used as the internal reference standard. The size of the ROIs was kept constant (radius 1.5 mm). Parametric color overlay maps were analyzed using ImageJ software (NIH, Bethesda, MD, USA).
2. Vascular Properties of Pediatric Brain Tumors Using Dynamic Contrast-enhanced MRI (DCE-MRI) After Administration of a Gadolinium-based Contrast Agent [ Time Frame: up to 2 years ]
   Volume transfer coefficient reflecting vascular permeability of pediatric brain tumors using Dynamic Contrast-enhanced MRI (DCE-MRI) was measured. Subjects undergo MRI with ferumoxytol (study drug) and gadolinium (standard contrast agent) in the same imaging session. Ferumoxytol is given first and DSC images obtained, followed by gadolinium, and DCE images are obtained.

Secondary Outcome Measures :

1. Histology (Only in Patients for Whom a Biopsy or Surgery is Scheduled Outside of This Protocol) [ Time Frame: Up to 2 years ]
   Appropriate descriptive statistics will be estimated. Results will be posted at overall completion.
2. Number of Enhancing Lesions [ Time Frame: Up to 2 years ]
   Appropriate descriptive statistics will be estimated. Results will be posted at overall completion.
3. Tumor Vascularity [ Time Frame: Up to 2 years ]
   Appropriate descriptive statistics will be estimated. Results will be posted at overall completion.
4. Ultrastructure (Only in Patients for Whom a Biopsy or Surgery is Scheduled Outside of This Protocol) [ Time Frame: Up to 2 years ]
   Appropriate descriptive statistics will be estimated. Results will be posted at overall completion.
5. Volume of Enhancing Lesions [ Time Frame: Up to 2 years ]
   Appropriate descriptive statistics will be estimated. Results will be posted at overall completion.

Eligibility Criteria

• Ages Eligible for Study: 5 Years to 18 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Participant must have either radiological (presumptive) or established (proven) histological diagnosis of a brain tumor or lesion
• Previously untreated participants must have a measureable lesion on an imaging study
• Participants undergoing active treatment, or who have completed treatment, will have radiographic abnormalities that may or may not be recurrent tumor
• Those participants requiring surgical intervention for diagnostic and/or therapeutic purposes as necessary for their disease are eligible; the tissue may be assessed by histology and/or EM for iron particles; only clinically indicated biopsy and/or surgery will be done
• Participants may have had prior therapy for the primary brain tumor, including surgery, radiotherapy or chemotherapy
• After entry into the study, participants agree to be followed for up to 6 weeks after the final infusion of ferumoxytol
• All participants, or their legal guardians, must sign a written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization in accordance with institutional guidelines
• Baseline MRI studies for participants receiving ferumoxytol must be performed within 16 weeks of study entry
• Sexually active women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; 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

Exclusion Criteria:

• Participants 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
• Participants with known allergic or hypersensitivity reactions to parenteral iron, parenteral dextran, parenteral iron-dextran, or parenteral iron-polysaccharide preparations, are not eligible; participants with significant drug or other allergies or autoimmune diseases may be enrolled at the Investigator's discretion
• Participants who are pregnant, lactating, or who suspect they might be pregnant are not eligible
• Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) greater than 2.5 x upper limits of normal
• Glomerular filtration rate (GFR) < 50
• Participants 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 GBCA
• Participants with known hepatic insufficiency or cirrhosis
• Human immunodeficiency virus (HIV)-positive participants on combination antiretroviral therapy are ineligible
• Participants that have a known or suspected iron overload (genetic hemochromatosis or history of multiple transfusions)

Contacts and Locations

Locations

United States, Oregon

OHSU Knight Cancer Institute

Portland, Oregon, United States, 97239

Sponsors and Collaborators

OHSU Knight Cancer Institute

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Edward Neuwelt; OHSU Knight Cancer Institute

More Information

• Responsible Party: Edward Neuwelt, Professor, OHSU Knight Cancer Institute
• ClinicalTrials.gov Identifier: NCT00978562
• Other Study ID Numbers: IRB00005405; NCI-2015-00227 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); 1562; 2864; SOL-09064-LX; 813; 5405 ( Other Identifier: OHSU Knight Cancer Institute ); P30CA069533 ( U.S. NIH Grant/Contract )
• First Posted: September 17, 2009
• Results First Posted: May 23, 2017
• Last Update Posted: February 1, 2018
• Last Verified: January 2018

Additional relevant MeSH terms:

Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Ferrosoferric Oxide; Hematinics; Parenteral Nutrition Solutions; Pharmaceutical Solutions