Pilot Study to Compare Dynamic MR Imaging Changes in Patients With Recurrent High Grade Glioma, Receiving an Antiangiogenic Drug, Bevacizumab, Versus Dexamethasone. Dual Agent MR Imaging Study, Using Gadolinium and Ferumoxytol (Code 7228)
18 Years
75 Years
Both
Brain Neoplasms
Trial Information
Pilot Study to Compare Dynamic MR Imaging Changes in Patients With Recurrent High Grade Glioma, Receiving an Antiangiogenic Drug, Bevacizumab, Versus Dexamethasone. Dual Agent MR Imaging Study, Using Gadolinium and Ferumoxytol (Code 7228)
Adult patients (>18 years old) with recurrent high grade glioma (confirmed by radiology and
tissue sample), who have progressed on prior temazolomide + radiation therapy, will be
recruited from the neurology, neurosurgery, or neuro-oncology clinics. Patients will be
enrolled if they meet the study inclusion and exclusion criteria
Patients will be scanned at four different time-points (4 MRI series) (1) before the
beginning of the treatment (base line), (2) Three weeks after the first treatment, (3) Three
weeks after the second treatment, and (4) at time of progression of the disease. Each MRI
time-point will consist of a series of MRI's on three consecutive days. On the first day,
gadolinium (0.1 mmol/kg) will be injected for the MRI scan. On the following day ferumoxytol
(2 mg/kg) and on the third day, the MRI scan will be done without additional contrast agent,
to see the delayed contrast enhancement of ferumoxytol.
Subjects will be on treatment including a chemotherapeutic agent called carboplatin combined
with either bevacizumab or dexamethasone; 6 patients will receive carboplatin-bevacizumab,
followed by carboplatin-dexamethasone, another 6 patients will receive carboplatin-
dexamethasone, followed by carboplatin-bevacizumab. After the 3rd time-point, all the
patients will continue on carboplatin-bevacizumab treatment (which is currently not an FDA
approved combination for brain tumors, however it is widely used throughout the
country).There will be monthly clinical visits with clinical MRI until progression of the
disease. There will be a follow up visit, 1 month after the last ferumoxytol injection.
Inclusion Criteria:
- Signed Informed Consent Form
- Age equal or greater than 18 years
- Histologically confirmed high grade glioma
- Radiographic demonstration of disease progression following prior therapy of
temozolomide + radiation
- Patient scheduled for bevacizumab + standard IV chemotherapy therapy
- Bi-dimensionally measurable disease on gadolinium enhanced T1 weighted MR scans
- An interval of at least 4 weeks since prior surgical resection
- Patients must be off corticosteroids at least 1 week before the start of the study
- Karnofsky performance status greater than or equal to 70
- Life expectancy greater than 12 weeks
- Ability to comply with study and follow-up procedures
Exclusion Criteria:
- Pregnant or nursing females
- 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
- Known liver function insufficiency, stage IV or V renal insufficiency
- Disease and Treatment History: Prior treatment with bevacizumab, or another VEGF or
VEGFR-targeted agent; Need for urgent palliative intervention for primary disease
(e.g., impending herniation
- Bevacizumab Exclusion Criteria: History of hypertensive encephalopathy; New York
Heart Association (NYHA) Grade II or greater CHF; History of myocardial infarction or
unstable angina within 6 months prior to start of the study; History of stroke or
transient ischemic attack within 6 months prior to study enrollment; Significant
vascular disease (e.g., aortic aneurysm, aortic dissection) or recent peripheral
arterial thrombosis within 6 months prior to start of the study; Evidence of bleeding
diathesis or coagulopathy; on therapeutic anti-coagulants.
- Subjects unable to undergo an MRI with contrast
- Ferumoxytol Exclusion Criteria: 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
- Subjects with known or suspected iron overload (genetic hemochromatosis or history of
multiple transfusions).Patients with transferrin saturation greater than 60%
- Inability or unwillingness to undergo the complete series of imaging sessions.
Inability or unwillingness to return to the neuro-oncology clinic at OHSU for the one
month follow-up
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Diagnostic
Outcome Measure:
The primary objective of this project is to describe quantitative imaging changes of brain tumor vascularity after anti-angiogenic therapy versus steroid therapy. This objective will be accomplished with the following aims and associated hypotheses.
Outcome Time Frame:
15 weeks
Safety Issue:
No
Principal Investigator
Edward A Neuwelt, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Oregon Health and Science University
Authority:
United States: Food and Drug Administration
Study ID:
OHSU-3678
NCT ID:
NCT00769093
Start Date:
October 2008
Completion Date:
February 2014
Related Keywords:
- Brain Neoplasms
- ferumoxytol
- diagnostic imaging
- Brain Neoplasms
- Neoplasms
Name | Location |
|---|---|
| Oregon Health & Science University | Portland, Oregon 97201 |
