Steady State Blood Volume Maps Using Ferumoxytol Non-stoichiometric Magnetite MRI in Imaging Patients With Glioblastoma

High Resolution Steady State Blood Volume Maps in Glioblastoma Using MRI - A Multicenter Study

This clinical trial studies steady state blood volume maps using ferumoxytol non-stoichiometric magnetite magnetic resonance (MRI) in imaging patients with glioblastoma. MRI is a procedure in which radio waves and a powerful magnet linked to a computer are used to create detailed pictures of areas inside the body. Contrast agents, such as ferumoxytol non-stoichiometric magnetite, may enhance these pictures and increase visibility of tumor cells and the blood vessels in and around the tumors.

Study Overview

• Status: Completed
• Conditions: Glioblastoma
• Intervention / Treatment: Drug: Ferumoxytol; Procedure: Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging; Drug: Gadoteridol; Procedure: Magnetic Resonance Imaging

Detailed Description

PRIMARY OBJECTIVE:

I. Testing if steady state (SS)-cerebral blood volume (CBV) maps are superior to dynamic susceptibility contrast-(DSC)-CBV maps in visualizing of brain tumor blood volumes.

SECONDARY OBJECTIVES:

I. Development of the SS-CBV mapping for quantitative CBV estimation. II. Assessment of therapeutic response. III. Association with survival. IV. Correlation of relative cerebral blood volume (rCBV) with histology. V. Assessment of late ferumoxytol (ferumoxytol non-stoichiometric magnetite) enhancement at various stages of disease.

OUTLINE:

Patients receive 2 doses (2nd dose optional) of gadoteridol intravenously (IV) and undergo MRI including DSC or dynamic contrast enhanced imaging (DCE)-CBV mapping over approximately 45-60 minutes on day 1. Within 3 days, patients receive 3 doses of ferumoxytol non-stoichiometric magnetite IV and undergo MRI including DSC and SS-CBV mapping after each dose over approximately 90 minutes. Patients undergo MRI without contrast 24 hours after ferumoxytol non-stoichiometric magnetite over approximately 30 minutes. This 2-3 day series of imaging repeats at different stages of disease and may be performed up to 5 times: prior to surgery, prior to chemoradiation therapy, 4-6 weeks post-chemoradiation therapy, at time of progression on gadolinium MRI per Response Assessment in Neuro-Oncology (RANO) criteria, and again at time of progression (if the previous time of progression showed pseudoprogression).

After completion of study, patients are followed up at 2 and 6 weeks.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University Comprehensive Cancer Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • OHSU Knight Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects must have a known or presumed radiological diagnosis of glioblastoma (GBM); for presumed diagnosis of GBM, histological confirmation of GBM must be completed within 12 weeks of enrollment; (subjects will be removed from study and non-evaluable if no histologic diagnosis of GBM is confirmed)
• Subjects must be enrolled before starting chemoradiation, either pre -or post-surgery
• 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 and men 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; 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 3 tesla (T) 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Diagnostic (DSC/DCE-CBV, SS-CBV mapping); Patients receive 2 doses (2nd dose optional) of gadoteridol IV and undergo MRI including DSC or DCE-CBV mapping over approximately 45-60 minutes on day 1. Within 3 days, patients receive 3 doses of ferumoxytol non-stoichiometric magnetite IV and undergo MRI including DSC and SS-CBV mapping after each dose over approximately 90 minutes. Patients undergo MRI without contrast 24 hours after ferumoxytol non-stoichiometric magnetite over approximately 30 minutes. This 3 day series of imaging repeats at different stages of disease and may be performed up to 5 times: prior to surgery, prior to chemoradiation therapy, 4-6 weeks post-chemoradiation therapy, at time of progression on gadolinium MRI per RANO criteria, and again at time of progression (if the previous time of progression showed pseudoprogression).

Drug: Ferumoxytol; Given IV; Other Names: Feraheme; Ferumoxytol Non-Stoichiometric Magnetite; Procedure: Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging; Undergo MRI including DSC or DCE-CBV mapping; Other Names: DSC-MRI; Dynamic Susceptibility Contrast-Enhanced MRI; DYNAMIC SUSCEPTIBILITY-CONTRAST MRI; Drug: Gadoteridol; Given IV; Other Names: ProHance; Gadoteridolum; GD-HP-DO3A; HSDB 7549; SQ 32692; Procedure: Magnetic Resonance Imaging; Undergo MRI including SS-CBV; Other Names: MRI; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR Imaging; MRI Scan; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of overlay accuracy with 3-dimensional (3D) anatomical T1w post contrast scans (MPRAGE)	Will be analyzed and the mean score between the two readers will be used in the primary analyses. That is, to compare steady state-cerebral blood volume (SS-CBV) maps and dynamic susceptibility contrast (DSC)-CBV maps, a linear mixed effects model will be used to compare the mean of the visualization variables between SS and DSC overall and at each of time points (before chemoradiation, after chemoradiation, at progression and after second line treatment) while taking into account the correlation due to repeated measures, and the clustering within institutions. Model assumptions will be evaluated and alternative models will be explored as necessary.	Up to 6 weeks after last visit
Confidence in identifying the lesion corresponding areas on cerebral blood volume (CBV) maps	Will be analyzed and the mean score between the two readers will be used in the primary analyses. That is, to compare steady state (SS)-CBV maps and dynamic susceptibility contrast (DSC)-CBV maps, a linear mixed effects model will be used to compare the mean of the visualization variables between SS and DSC overall and at each of time points (before chemoradiation, after chemoradiation, at progression and after second line treatment) while taking into account the correlation due to repeated measures, and the clustering within institutions. Model assumptions will be evaluated and alternative models will be explored as necessary.	Up to 6 week after last visit
Assessment of cerebral blood volume (CBV) in small (< 1 cm) enhancing lesions	Will be analyzed and the mean score between the two readers will be used in the primary analyses. That is, to compare steady state (SS)-CBV maps and dynamic susceptibility contrast (DSC)-CBV maps, a linear mixed effects model will be used to compare the mean of the visualization variables between SS and DSC overall and at each of time points (before chemoradiation, after chemoradiation, at progression and after second line treatment) while taking into account the correlation due to repeated measures, and the clustering within institutions. Model assumptions will be evaluated and alternative models will be explored as necessary.	Up to 6 weeks after the last visit
Delineation of tumor from larger blood vessels	Will be analyzed and the mean score between the two readers will be used in the primary analyses. That is, to compare steady state-cerebral blood volume (SS-CBV) maps and dynamic susceptibility contrast (DSC)-CBV maps, a linear mixed effects model will be used to compare the mean of the visualization variables between SS and DSC overall and at each of time points (before chemoradiation, after chemoradiation, at progression and after second line treatment) while taking into account the correlation due to repeated measures, and the clustering within institutions. Model assumptions will be evaluated and alternative models will be explored as necessary.	Up to 6 weeks after last visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	For the assessment of therapeutic response and association with survival, the cerebral blood volume (CBV) values will be correlated with survival using a Cox mixed effects regression model while adjusting patient demographical and clinical characteristics and the clustering within institutions. To determine at which stage of the disease the steady state CBV will best predict survival as well as the best cut off points, separate models will be fit for different disease stages and different cutoff points including 1.75, others and the Response Assessment in Neuro-Oncology (RANO) criteria.	Up to 6 weeks after last visit
Relative cerebral blood volume (rCBV) values	A linear model will be used to assess correlation of rCBV with histology based on the availability of data.	Up to 6 weeks after last visit
Ferumoxytol enhancement	A linear mixed effects regression model will first be used to examine the relationship between transverse relaxation rate and ferumoxytol doses while taking the correlation due to repeated measures into account. If the relationship between transverse relaxation rate and ferumoxytol doses does not show good linearity, alternative function forms will be tested, for example, polynomial or exponential.	24 hours after ferumoxytol administration

Collaborators and Investigators

• Sponsor: OHSU Knight Cancer Institute
• Collaborators: Oregon Health and Science University
• Investigators: Principal Investigator: Edward A Neuwelt, OHSU Knight Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): January 6, 2015
• Primary Completion (Actual): March 12, 2021
• Study Completion (Actual): March 12, 2021

Study Registration Dates

• First Submitted: February 4, 2015
• First Submitted That Met QC Criteria: February 4, 2015
• First Posted (Estimate): February 9, 2015

Study Record Updates

• Last Update Posted (Actual): March 17, 2022
• Last Update Submitted That Met QC Criteria: March 11, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Hematinics; Pharmaceutical Solutions; Parenteral Nutrition Solutions; Ferrosoferric Oxide
• Other Study ID Numbers: IRB00009846 (Other Identifier: OHSU Knight Cancer Institute); NCI-2015-00080 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); SOL-13090-L; eIRB#9846