Childhood Brain Neoplasm, Recurrent Childhood Brain Neoplasm
Conditions
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.
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.
Interventions
PROCEDUREDynamic Contrast-Enhanced Magnetic Resonance Imaging
Undergo DCE-MRI
Undergo DSC-MRI
Given IV
DRUGGadolinium
Given IV
Sponsors
National Cancer Institute (NCI)
OHSU Knight Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
5 Years to 18 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Vascular Properties of Pediatric Brain Tumors Using Dynamic Susceptibility-weighted Contrast Enhanced MRI (DSC-MRI) After Administration of Ferumoxytol | 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). |
| Vascular Properties of Pediatric Brain Tumors Using Dynamic Contrast-enhanced MRI (DCE-MRI) After Administration of a Gadolinium-based Contrast Agent | 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
| Measure | Time frame | Description |
|---|---|---|
| Tumor Vascularity | Up to 2 years | Appropriate descriptive statistics will be estimated. Results will be posted at overall completion. |
| Histology (Only in Patients for Whom a Biopsy or Surgery is Scheduled Outside of This Protocol) | Up to 2 years | Appropriate descriptive statistics will be estimated. Results will be posted at overall completion. |
| Volume of Enhancing Lesions | Up to 2 years | Appropriate descriptive statistics will be estimated. Results will be posted at overall completion. |
| Ultrastructure (Only in Patients for Whom a Biopsy or Surgery is Scheduled Outside of This Protocol) | Up to 2 years | Appropriate descriptive statistics will be estimated. Results will be posted at overall completion. |
| Number of Enhancing Lesions | Up to 2 years | Appropriate descriptive statistics will be estimated. Results will be posted at overall completion. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
Dynamic Contrast-Enhanced Magnetic Resonance Imaging: Undergo DCE-MRI
Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging: Undergo DSC-MRI
Ferumoxytol Non-Stoichiometric Magnetite: Given IV
Gadolinium: Given IV | 14 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by participant before receiving study drug/imaging | 2 |
Baseline characteristics
| Characteristic | Diagnostic (DSC-MRI With Ferumoxytol, DCE-MRI With Gadolinium) |
|---|---|
| Age, Continuous | 10.64 years STANDARD_DEVIATION 3.33 |
| Region of Enrollment United States | 14 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 14 |
| other Total, other adverse events | 8 / 14 |
| serious Total, serious adverse events | 2 / 14 |
Outcome results
Primary
Vascular Properties of Pediatric Brain Tumors Using Dynamic Contrast-enhanced MRI (DCE-MRI) After Administration of a Gadolinium-based Contrast Agent
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.
Time frame: up to 2 years
Population: 7 participants had both appropriate ferumoxytol and gadolinium scans available for analysis for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ferumoxytol DSC MRI | Vascular Properties of Pediatric Brain Tumors Using Dynamic Contrast-enhanced MRI (DCE-MRI) After Administration of a Gadolinium-based Contrast Agent | .25 min^-1 | Standard Deviation 0.23 |
Primary
Vascular Properties of Pediatric Brain Tumors Using Dynamic Susceptibility-weighted Contrast Enhanced MRI (DSC-MRI) After Administration of Ferumoxytol
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).
Time frame: Up to 2 years
Population: 7 participants had both appropriate ferumoxytol and gadolinium scans available for analysis for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ferumoxytol DSC MRI | Vascular Properties of Pediatric Brain Tumors Using Dynamic Susceptibility-weighted Contrast Enhanced MRI (DSC-MRI) After Administration of Ferumoxytol | .93 mL/g | Standard Deviation 1.44 |
Secondary
Histology (Only in Patients for Whom a Biopsy or Surgery is Scheduled Outside of This Protocol)
Appropriate descriptive statistics will be estimated. Results will be posted at overall completion.
Time frame: Up to 2 years
Population: Due to low enrollment and staffing issues, data was not collected for this outcome.
Secondary
Number of Enhancing Lesions
Appropriate descriptive statistics will be estimated. Results will be posted at overall completion.
Time frame: Up to 2 years
Population: Due to low enrollment and staffing issues, data was not collected for this outcome.
Secondary
Tumor Vascularity
Appropriate descriptive statistics will be estimated. Results will be posted at overall completion.
Time frame: Up to 2 years
Population: Due to low enrollment and staffing issues, data was not collected for this outcome.
Secondary
Ultrastructure (Only in Patients for Whom a Biopsy or Surgery is Scheduled Outside of This Protocol)
Appropriate descriptive statistics will be estimated. Results will be posted at overall completion.
Time frame: Up to 2 years
Population: Due to low enrollment and staffing issues, data was not collected for this outcome.
Secondary
Volume of Enhancing Lesions
Appropriate descriptive statistics will be estimated. Results will be posted at overall completion.
Time frame: Up to 2 years
Population: Due to low enrollment and staffing issues, data was not collected for this outcome.