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

NCT00769093 | Terminated Phase 1 DMC

• 5 other identifiers: IRB0000367826XS2933678SOL-07083-LXOHSU-3678
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Brain Neoplasms

Keywords

ferumoxytol; diagnostic imaging

Outcome Measures

Primary Outcomes (3)

• 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.

  15 weeks

• To describe changes of quantitative blood brain barrier permeability measurements (Ktrans) of a standard gadolinium (Gd) MRI contrast between bevacizumab anti-angiogenic therapy and dexamethasone.

  15 weeks

• To describe relative cerebral blood volume (rCBV) changes obtained using ferumoxytol an iron oxide nanoparticle blood pool agent.

  15 weeks

Secondary Outcomes (3)

• To assess vascular dynamic parameters (rCBV and Ktrans) values at progression.

  at progression

• To describe the changes of the vascular dynamic parameters (rCBV, Ktrans) with the changes of standard gadolinium enhancing tumor volume

  15 weeks

• To describe post contrast tumor volume (enhancement) of gadolinium and ferumoxytol.

  15 weeks

Study Arms (2)

Group 1

ACTIVE COMPARATOR

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.

Drug: Ferumoxytol

Group 2

ACTIVE COMPARATOR

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.

Drug: Ferumoxytol

Interventions

Ferumoxytol DRUG

2 mg/kg

Also known as: AMAG Pharmaceuticals, Inc., Code 7228

Group 1; Group 2

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead
• National Cancer Institute (NCI): collaborator
• AMAG Pharmaceuticals, Inc.: collaborator

Study Sites (1)

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

MeSH Terms

Conditions

Brain Neoplasms

Interventions

Ferrosoferric Oxide

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Ferric Compounds; Iron Compounds; Inorganic Chemicals; Ferrous Compounds; Minerals

Study Officials

• Edward A Neuwelt, MD

  Oregon Health and Science University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 7, 2008
• First Posted: October 8, 2008
• Study Start: October 1, 2008
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: April 21, 2017

Record last verified: 2017-04

Locations

US (1)