Imaging of Intravenous (IV) Combidex to Brain, Intra-cerebral Tumors and in Central Nervous System (CNS) Inflammation

Phase 2

Terminated

Conditions: Brain Neoplasms

Interventions: Drug: Ferumoxtran-10 (Combidex)
Procedure: Neurosurgery

Registration Number: NCT00659334

Lead Sponsor: OHSU Knight Cancer Institute

Brief Summary: Combidex (ferumoxtran-10) is an ultra-small iron oxide particle covered with a sugar coating. It has been evaluated as an MRI contrast agent for use in imaging well perfused organs such as the liver and spleen and for imaging lymph nodes. In this study, Combidex is being used to compare the standard imaging agent, Gadolinium, in imaging brain tumors and the area adjacent to the tumor location. Combidex may provide the ability to better see brain tumors and inflammatory lesions on magnetic resonance imaging (MRI) scans. Combidex may be useful in its ability to cross blood vessels into brain tumors, and because of its size and ability to get into the area next to brain tumors, could assist in the treatment of brain tumors with other drugs in the future.

Detailed Description: Subjects are recruited as patients in one of the neurology, neurosurgery or neuro-oncology clinics at OHSU. There are four groups of the study:

* Subjects receive the combidex infusion only.

* Subjects receive Combidex and undergo a previously schedule neurosurgery.

* Subjects undergo surgery only and provide a sample of their tumor tissue to be used in pathology studies of Combidex.

* Subjects with MS or stroke are invited to participate in receiving Combidex to evaluate the effectiveness of enhancing the area of damage within the brain.

Subjects are deemed eligible for the study and undergo a baseline MRI within 28 days of receiving Combidex. Subjects receiving Combidex are admitted for a half day into the Oregon Clinical \& Translational Research Institute(OCTRI). Combidex is infused I.V. over 30 minutes. Subjects are monitored for side effects and are discharged within about 5 hours after the infusion, if no complications have been noted. Subjects return 24 hours after the infusion for a post infusion MRI scan and return again to one of the neurology clinics for one month follow-up. Subjects enrolled in group 2 undergo surgery 1-2 days after the Combidex infusion and also undergo a 24 post infusion MRI and return for one month follow-up. These subjects are also followed closely by the neurosurgical physician during the course of follow-up. Subjects enrolled in group 3 only undergo surgery and agree to have a piece of their tumor resection or biopsy donated for use in the study. Group 4 is the same as group 1, except the patient population includes multiple sclerosis and stroke instead of patients with brain tumors.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 116

Inclusion Criteria

Brain tumor or CNS inflammatory lesion including stroke or MS
5 yrs old or older
Able to undergo MRI without general anesthesia
Agree to be followed for 1 month following infusion of Combidex
Sign a written informed consent
If female and of child-bearing potential, be postmenopausal, sterile, or be on birth control for 1 month prior to study
Must have a pre-treatment MRI within 28 days before study

Exclusion Criteria

Clinically significant signs of uncal herniation
Allergy to study drug, Combidex
Hepatic insufficiency
Stage IV or V renal insufficiency
If female, pregnant or lactating
Require anesthesia for MRI scanning
Hemachromatosis

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
4	Ferumoxtran-10 (Combidex)	Children with brain tumors to receive Combidex only
5	Neurosurgery	Children with brain tumors to receive Combidex and neurosurgery
1	Ferumoxtran-10 (Combidex)	Adults with brain tumor to receive Combidex infusion only
3	Neurosurgery	Adults with brain tumors to receive neurosurgery only (NO Combidex)
5	Ferumoxtran-10 (Combidex)	Children with brain tumors to receive Combidex and neurosurgery
2	Ferumoxtran-10 (Combidex)	Adults with brain tumors to receive Combidex infusion and neurosurgery
7	Ferumoxtran-10 (Combidex)	Adults with Inflammatory lesions (stroke or MS) to receive Combidex only
2	Neurosurgery	Adults with brain tumors to receive Combidex infusion and neurosurgery
6	Neurosurgery	Children with brain tumors to receive neurosurgery only, NO Combidex

Primary Outcome Measures

Name	Time	Method
Number of Participants Who Experience Optimal Imaging in Adult and Pediatric Brain Tumors to Establish Timing and Sequencing Parameters of Combidex.	24 hours (some patients between 3 and 72 hours) after administration of Combidex	Signal intensity change in participants with Pre and 24 hours Post Combidex on T1, T2, T2\* MRI sequences will be assessed (some patients undergo scans at 3 and 72 hours in order to assess radiographic changes at these time points). Combidex will be administered in dose 2.6 mg/kg in adults with high and low grade gliomas, metastases, meningiomas, and PNET; and in pediatric patients with astrocytomas grade i-iv, brain stem gliomas, ependymomas, CNS germ cell tumors, and PNET.

Secondary Outcome Measures

Name	Time	Method
Compare Pre- and Post-op Gd Enhanced MRI Combidex Enhanced MR Imaging Done Pre-, Intra- and Post-operatively, to Assess the Degree of Resection and Residual Tumor.	2 years
Compare Combidex Imaging in Brain Tumor Patients, With Other CNS Inflammatory Lesions Such as Multiple Sclerosis and Stroke.	2 years
Assess the Cellular Uptake of Particles in Brain Tumor Patients by Comparing Imaging Results With Histology and Electron Microscopic Examination of Biopsy Tissue	2 years