Assessing Dynamic Magnetic Resonance (MR) Imaging in Patients With Recurrent High Grade Glioma Receiving Chemotherapy

NCT ID: NCT00769093

Last Updated: 2017-04-21

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-10-31
• Study Completion Date: 2014-07-31

Brief Summary

The purpose of this study is to learn more about imaging changes induced by a new therapeutic agent, bevacizumab with the standard steroid, dexamethasone in patients with high grade glioma. Magnetic resonance imaging (MRI) will be used to evaluate the difference between the 2 treatments. The usual contrast agent (gadolinium) and an iron containing contrast agent called "ferumoxytol" may help us to evaluate the differences between bevacizumab and dexamethasone effects on imaging of a brain tumor called high grade glioma. For this purpose, after intravenous contrast agent injection, special MR scans (called: dynamic perfusion, blood-brain barrier (BBB) permeability measurement) will be performed to see the microvascular changes in the brain and tumor.

Detailed Description

Adult patients (>18 years old) with recurrent high grade glioma (confirmed by radiology and tissue sample), who have progressed on prior temozolomide + 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.

Conditions

Brain Neoplasms

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Group 1

Both groups will receive an intravenous chemotherapeutic drug (carboplatin). The first study group (n=6) will receive bevacizumab, the antiangiogenic agent for three weeks, then dexamethasone for three weeks.

Group Type: ACTIVE_COMPARATOR

Ferumoxytol

Intervention Type: DRUG

2 mg/kg

Group 2

Both groups will receive an intravenous chemotherapeutic drug (carboplatin). The second study group (n=6) will receive dexamethasone for 3 weeks, then switch to bevacizumab, the antiangiogenic agent, for 3 weeks.

Group Type: ACTIVE_COMPARATOR

Ferumoxytol

Intervention Type: DRUG

2 mg/kg

Interventions

Ferumoxytol

2 mg/kg

Intervention Type: DRUG

Other Intervention Names

AMAG Pharmaceuticals, Inc., Code 7228

Eligibility Criteria

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 corticosteroid dose must be 4 mg per day or less.
• Karnofsky performance status greater than or equal to 50
• 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 vascular endothelial growth factor (VEGF) or VEGFR-targeted agent; Need for urgent palliative intervention for primary disease (e.g., impending herniation
• Subjects unable to undergo an MRI with contrast
• 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 Oregon Health and Science University (OHSU) for the one month follow-up

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

AMAG Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: collaborator

OHSU Knight Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Edward Neuwelt

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Edward A Neuwelt, MD

Role: PRINCIPAL_INVESTIGATOR

Oregon Health and Science University

Locations

Oregon Health & Science University

Portland, Oregon, United States

Countries

United States

Other Identifiers

26XS293

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

3678

Identifier Type: OTHER

Identifier Source: secondary_id

SOL-07083-LX

Identifier Type: OTHER

Identifier Source: secondary_id

OHSU-3678

Identifier Type: OTHER

Identifier Source: secondary_id

IRB00003678

Identifier Type: -

Identifier Source: org_study_id