Magnetic Resonance (MR) Imaging Study Using Ferumoxytol to Assess Early Tumor Response in Patients With Glioblastoma Multiforme

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by OHSU Knight Cancer Institute
Sponsor:
Collaborator:
Information provided by (Responsible Party):
OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier:
NCT00660543
First received: April 10, 2008
Last updated: May 9, 2014
Last verified: May 2014
  Purpose

In this study the investigators would like to find out how a new iron containing Magnetic Resonance Imaging (MRI) contrast agent, called "ferumoxytol" can help the investigators to assess at the beginning of a therapy if it is effective or not in the treatment of a brain tumor called Glioblastoma Multiforme (GBM). For this purpose, after intravenous ferumoxytol injection, special MR scans (called: dynamic perfusion, blood-brain barrier (BBB) permeability measurement) will be performed to see the vascular changes in the brain and tumor.


Condition Intervention Phase
Diagnostic Imaging
Drug: Ferumoxytol
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Early Assessment of Tumor Response to Therapy Using Ferumoxytol (Code 7228) as an MR Contrast Agent in Patients With Glioblastoma Multiforme

Resource links provided by NLM:


Further study details as provided by OHSU Knight Cancer Institute:

Primary Outcome Measures:
  • To characterize GBM tumor vascular properties using Ferumoxytol and compare to those obtained using Gd based MRI contrast agent. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Comparison of Gd and Ferumoxytol contrast agents for assessing cerebral blood flow , mean transit time , and time-to-peak perfusion parameters, and evaluate if any of these perfusion parameters is promising for tracking GBM therapeutic response. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • To obtain qualitative assessment of tumor vascularity using time-of-flight(TOF) MR angiography techniques. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • To characterize changes in the apparent diffusion coefficient (ADC) of tumor water associated with standard radio/chemotherapy in GBM. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 12
Study Start Date: October 2006
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Patients will be scanned at four time-points of their radiation/temozolomide treatment: before onset of radiation/temozolomide treatment, at 3 weeks, 6 weeks and 12 weeks following the onset of treatment. Each time-point will consist of three visits on three consecutive days. On first day: MRI with and without gadolinium (the usual MR contrast agent) infusion (0.1 mmol/kg). On second day: MRI with ferumoxytol infusion (1 mg/kg). On the third day: MRI without additional contrast agent, 24 hr post ferumoxytol infusion. There will be follow up visits 1 month and 6 months after the last ferumoxytol injection
Drug: Ferumoxytol

The ferumoxytol will be injected as an IV bolus of 2 mg Fe/kg over approximately 2-4 seconds at 4 ml/s flow rate, followed by a saline flush, at four time points:

2 mg/kg before, after 3 weeks of the initiation of radiation plus temozolomide, at the end of radiation (6 weeks post first dose) and 6 weeks after radiation (12 weeks post first dose). Cumulative ferumoxytol dose is 8 mg/kg about the half of the iron therapy dose (2 x 510 mg).


Detailed Description:

Patients will be scanned at four time-points of their radiation/temozolomide treatment: before onset of radiation/temozolomide treatment, at 3 weeks, 6 weeks and 12 weeks following the onset of treatment. Each time-point will consist of three visits on three consecutive days. On first day: MRI with and without gadolinium (the usual MR contrast agent) infusion (0.1 mmol/kg). On second day: MRI with ferumoxytol infusion (1 mg/kg). On the third day: MRI without additional contrast agent, 24 hr post ferumoxytol infusion. There will be follow up visits 1 month and 6 months after the last ferumoxytol injection.

The ferumoxytol molecule contains iron-oxide and other components (carbohydrate), which makes ferumoxytol safe for short and fast (bolus) injections. This new contrast agent has not shown significant side effects, even using extremely high doses in animal experiments. A total of 516 human subjects have received one or more doses of ferumoxytol. There have been 3 cases with serious side effects possibly related to the administration of ferumoxytol. Two cases of peritonitis (the inflammation of the lining the abdomen) that were possibly related and one case of anaphylaxis (serious allergic reaction) related to ferumoxytol. (Of note is that gadolinium, the standard contrast agent, carries a serious risk for persons with kidney dysfunction. This risk is the condition called nephrogenic systemic fibrosis (NSF), which causes scar tissue to develop and can, in some cases, affect internal organs and even lead to death.)

The various types of MR measurement (Perfusion, blood-brain barrier permeability, diffusion) will be evaluated or measured at each time-point, for each contrast agent. Certain regions will be described and the data will be evaluated throughout the study in an attempt to correlate changes with tumor response to therapy. The tumor volume will be evaluated by 2 radiologists, measuring the diameters of the largest areas of contrast enhancement and signal intensities will be also compared (semi-quantitatively).

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have radiologically and histologically confirmed diagnosis of glioblastoma multiforme
  • Patients must have measurable disease, defined as evident tumors with gadolinium enhancement on MRI that is measurable in at least one diameter and visible on both axial and sagittal or coronal views.
  • Patients have not had prior chemotherapy and/or radiotherapy
  • Life expectancy of greater than 6 months
  • Eastern Cooperative Oncology Group (ECOG) performance status > or = 2 (Karnofsky > or =60%)
  • Patients scheduled for standard therapy (6 weeks RT ~60 gray (Gy), plus temozolomide 75 mg/m2 during 6w RT, 200 mg/m2 5x wk post RT started 4wk after RT)
  • Patients must be on a stable dose (up to 8mg daily) of dexamethasone throughout the study.
  • After entry into the study, patients are expected to be followed for at least 1 month after the last infusion of ferumoxytol
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.
  • Ability to understand and the willingness to sign a written informed consent document. All patients, or their legal guardians, must sign a written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization in accordance with institutional guidelines.

Exclusion Criteria:

  • Patients who have had chemotherapy or radiotherapy.
  • Patients may not be receiving any other investigational agents.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to ferumoxytol: parenteral iron, parenteral dextran, parenteral iron-dextran, or parenteral iron-polysaccharide preparations (Ferumoxytol Investigator's Drug Brochure, 2005). Patients with significant drug or other allergies or autoimmune diseases may be enrolled at the Investigator's discretion.
  • Patients with clinically significant signs of uncal herniation, such as acute pupillary enlargement, rapidly developing motor changes (over hours), or rapidly decreasing level of consciousness.
  • Patients who require monitored anesthesia for MRI scanning
  • Patient with history of hemochromatosis or iron overload
  • Patients with stage IV or V renal insufficiency
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant women are excluded from this study. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ferumoxytol, breastfeeding should be discontinued if the mother is treated with ferumoxytol
  • HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with ferumoxytol.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00660543

Contacts
Contact: Edward A Neuwelt, MD 503-494-5626 neuwelte@ohsu.edu
Contact: Cynthia A Lacy, BSN 503-494-5626 lacyc@ohsu.edu

Locations
United States, Oregon
Oregon Health & Science University Recruiting
Portland, Oregon, United States, 97239
Contact: Edward A Neuwelt, MD    503-494-5626    neuwelte@ohsu.edu   
Principal Investigator: Edward A Neuwelt, MD         
Sponsors and Collaborators
OHSU Knight Cancer Institute
Investigators
Principal Investigator: Edward A Neuwelt, MD Oregon Health and Science University
  More Information

No publications provided

Responsible Party: OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier: NCT00660543     History of Changes
Other Study ID Numbers: OHSU-2753, 26XS293, 2753, SOL-06062-LX
Study First Received: April 10, 2008
Last Updated: May 9, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by OHSU Knight Cancer Institute:
ferumoxytol

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Contrast Media
Ferrosoferric Oxide
Diagnostic Uses of Chemicals
Pharmacologic Actions
Hematinics
Hematologic Agents
Therapeutic Uses
Parenteral Nutrition Solutions
Pharmaceutical Solutions

ClinicalTrials.gov processed this record on September 22, 2014