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

Primary Purpose

Brain Neoplasms

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Ferumoxytol

About this trial

This is an interventional diagnostic trial for Brain Neoplasms focused on measuring ferumoxytol, diagnostic imaging

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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
Bevacizumab Exclusion Criteria: History of hypertensive encephalopathy; New York Heart Association (NYHA) Grade II or greater congestive heart failure (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 Oregon Health and Science University (OHSU) for the one month follow-up

Sites / Locations

Oregon Health & Science University

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Group 1

Group 2

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

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.

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

Secondary Outcome Measures

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

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

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

Full Information

NCT ID

NCT00769093

First Posted

October 7, 2008

Last Updated

April 19, 2017

Sponsor

OHSU Knight Cancer Institute

Collaborators

National Cancer Institute (NCI), AMAG Pharmaceuticals, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT00769093

Brief Title

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

Official Title

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)

Study Type

Interventional

2. Study Status

Record Verification Date

April 2017

Overall Recruitment Status

Terminated

Why Stopped

Inadequate enrollment

Study Start Date

October 2008 (undefined)

Primary Completion Date

July 2014 (Actual)

Study Completion Date

July 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

OHSU Knight Cancer Institute

Collaborators

National Cancer Institute (NCI), AMAG Pharmaceuticals, Inc.

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Brain Neoplasms

Keywords

ferumoxytol, diagnostic imaging

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

6 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Group 1

Arm Type

Active Comparator

Arm Description

Arm Title

Group 2

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Ferumoxytol

Other Intervention Name(s)

AMAG Pharmaceuticals, Inc., Code 7228

Intervention Description

2 mg/kg

Primary Outcome Measure Information:

Title

Time Frame

15 weeks

Title

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.

Time Frame

15 weeks

Title

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

Time Frame

15 weeks

Secondary Outcome Measure Information:

Title

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

Time Frame

at progression

Title

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

Time Frame

15 weeks

Title

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

Time Frame

15 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

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 Bevacizumab Exclusion Criteria: History of hypertensive encephalopathy; New York Heart Association (NYHA) Grade II or greater congestive heart failure (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 Oregon Health and Science University (OHSU) for the one month follow-up

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Edward A Neuwelt, MD

Organizational Affiliation

Oregon Health and Science University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Oregon Health & Science University

City

Portland

State/Province

Oregon

ZIP/Postal Code

97239

Country

United States

12. IPD Sharing Statement

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

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