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

• ClinicalTrials.gov Identifier: NCT00659334
• Recruitment Status: Terminated
• First Posted: April 16, 2008
• Results First Posted: November 9, 2012
• Last Update Posted: May 16, 2017
• Sponsor: OHSU Knight Cancer Institute
• Collaborators: National Institutes of Health (NIH); National Institute of Neurological Disorders and Stroke (NINDS)
• Information provided by (Responsible Party): Edward Neuwelt, OHSU Knight Cancer Institute

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Brain Neoplasms	Drug: Ferumoxtran-10 (Combidex); Procedure: Neurosurgery	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 116 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Multi-disciplinary Study: MR, Histologic and EM Imaging of Intravenous Superparamagnetic Crystalline Particles (Combidex) to Brain, Intra-cerebral Tumors and in CNS Inflammation
• Study Start Date: August 2000
• Actual Primary Completion Date: March 2010
• Actual Study Completion Date: March 2010

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: 1; Adults with brain tumor to receive Combidex infusion only	Drug: Ferumoxtran-10 (Combidex); 2.6 mg/kg; Other Name: Combidex
Active Comparator: 2; Adults with brain tumors to receive Combidex infusion and neurosurgery	Drug: Ferumoxtran-10 (Combidex); 2.6 mg/kg; Other Name: Combidex; Procedure: Neurosurgery; neuro-surgical tumor biopsy or resection to assess particle localization. Biopsy (stereotactic, when possible) will take place following the 24 hour post- Combidex MR and within 48 hrs of i.v. Combidex administration. Biopsies will be taken from the tumor, brain around tumor (BAT) and brain distant to tumor and the MR localization and histology will be compared. The tissue will be obtained by either resection or needle frameless stereotactic biopsy.
3; Adults with brain tumors to receive neurosurgery only (NO Combidex)	Procedure: Neurosurgery; neuro-surgical tumor biopsy or resection to assess particle localization. Biopsy (stereotactic, when possible) will take place following the 24 hour post- Combidex MR and within 48 hrs of i.v. Combidex administration. Biopsies will be taken from the tumor, brain around tumor (BAT) and brain distant to tumor and the MR localization and histology will be compared. The tissue will be obtained by either resection or needle frameless stereotactic biopsy.
Active Comparator: 4; Children with brain tumors to receive Combidex only	Drug: Ferumoxtran-10 (Combidex); 2.6 mg/kg; Other Name: Combidex
Active Comparator: 5; Children with brain tumors to receive Combidex and neurosurgery	Drug: Ferumoxtran-10 (Combidex); 2.6 mg/kg; Other Name: Combidex; Procedure: Neurosurgery; neuro-surgical tumor biopsy or resection to assess particle localization. Biopsy (stereotactic, when possible) will take place following the 24 hour post- Combidex MR and within 48 hrs of i.v. Combidex administration. Biopsies will be taken from the tumor, brain around tumor (BAT) and brain distant to tumor and the MR localization and histology will be compared. The tissue will be obtained by either resection or needle frameless stereotactic biopsy.
6; Children with brain tumors to receive neurosurgery only, NO Combidex	Procedure: Neurosurgery; neuro-surgical tumor biopsy or resection to assess particle localization. Biopsy (stereotactic, when possible) will take place following the 24 hour post- Combidex MR and within 48 hrs of i.v. Combidex administration. Biopsies will be taken from the tumor, brain around tumor (BAT) and brain distant to tumor and the MR localization and histology will be compared. The tissue will be obtained by either resection or needle frameless stereotactic biopsy.
Active Comparator: 7; Adults with Inflammatory lesions (stroke or MS) to receive Combidex only	Drug: Ferumoxtran-10 (Combidex); 2.6 mg/kg; Other Name: Combidex

Outcome Measures

Primary Outcome Measures :

1. Number of Participants Who Experience Optimal Imaging in Adult and Pediatric Brain Tumors to Establish Timing and Sequencing Parameters of Combidex. [ Time Frame: 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 :

1. Assess the Cellular Uptake of Particles in Brain Tumor Patients by Comparing Imaging Results With Histology and Electron Microscopic Examination of Biopsy Tissue [ Time Frame: 2 years ]
2. Compare Combidex Imaging in Brain Tumor Patients, With Other CNS Inflammatory Lesions Such as Multiple Sclerosis and Stroke. [ Time Frame: 2 years ]
3. 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. [ Time Frame: 2 years ]

Eligibility Criteria

• Ages Eligible for Study: 5 Years to 75 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Oregon

Oregon Health & Science University

Portland, Oregon, United States, 97239

Sponsors and Collaborators

OHSU Knight Cancer Institute

National Institutes of Health (NIH)

National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

• Principal Investigator: Edward A Neuwelt, MD; Oregon Health and Science University

More Information

• Responsible Party: Edward Neuwelt, Professor, OHSU Knight Cancer Institute
• ClinicalTrials.gov Identifier: NCT00659334
• Other Study ID Numbers: IRB00001127; 5R01NS034608 ( U.S. NIH Grant/Contract ); OHSU-1127 ( Other Identifier: OHSU IRB )
• First Posted: April 16, 2008
• Results First Posted: November 9, 2012
• Last Update Posted: May 16, 2017
• Last Verified: April 2017

Keywords provided by Edward Neuwelt, OHSU Knight Cancer Institute:

Combidex; Diagnostic imaging

Additional relevant MeSH terms:

Brain Neoplasms; Inflammation; Pathologic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases