Brain Neoplasms
Conditions
Keywords
Combidex, Diagnostic imaging
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.
Interventions
DRUGFerumoxtran-10 (Combidex)
2.6 mg/kg
PROCEDURENeurosurgery
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.
Sponsors
National Institutes of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
OHSU Knight Cancer Institute
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
5 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 |
| Compare Combidex Imaging in Brain Tumor Patients, With Other CNS Inflammatory Lesions Such as Multiple Sclerosis and Stroke. | 2 years |
| 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 |
Countries
United States
Participant flow
Recruitment details
Subjects are recruited as patients in one of the neurology, neurosurgery or neuro-oncology clinics at OHSU.
Pre-assignment details
There are seven groups in the study. In Groups 1(adults) and 4(pediatric) subjects receive the Combidex infusion only. In Groups 2(adult) and 5(pediatrics) subjects receive Combidex and undergo neurosurgery. In Groups 3(adult) and 6(pediatric) subjects undergo surgery with tissue exam; and in Group 7(adult only) subjects with MS or stroke.
Participants by arm
| Arm | Count |
|---|---|
| Combidex Only (Group 1) Adults with brain tumor to receive Combidex infusion only | 46 |
| Combidex and Neurosurgery (Group 2) Adults with brain tumors to receive Combidex infusion and neurosurgery | 41 |
| Neurosurgery Only (Group 3) Adults with brain tumors to receive neurosurgery only (NO Combidex) | 5 |
| Combidex Only (Group 4) Children with brain tumors to receive Combidex only | 2 |
| Combidex and Neurosurgery (Group 5) Children with brain tumors to receive Combidex and neurosurgery | 1 |
| Neurosurgery Only (Group 6) Children with brain tumors to receive neurosurgery only, NO Combidex | 0 |
| Inflammatory Lesions (Group 7) Adults with Inflammatory lesions (stroke or MS) to receive Combidex only | 21 |
| Total | 116 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Screen Failure | 8 | 5 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Combidex Only (Group 1) | Combidex and Neurosurgery (Group 2) | Neurosurgery Only (Group 3) | Combidex Only (Group 4) | Combidex and Neurosurgery (Group 5) | Inflammatory Lesions (Group 7) |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants |
| Age, Categorical >=65 years | 17 Participants | 9 Participants | 6 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 96 Participants | 37 Participants | 35 Participants | 5 Participants | 0 Participants | 0 Participants | 19 Participants |
| Age, Continuous | 48.8 years STANDARD_DEVIATION 15.1 | 52.3 years STANDARD_DEVIATION 13.2 | 48.4 years STANDARD_DEVIATION 12.8 | 45.4 years STANDARD_DEVIATION 14.2 | 14.7 years STANDARD_DEVIATION 1.4 | 14.1 years STANDARD_DEVIATION 0 | 43.0 years STANDARD_DEVIATION 15.3 |
| Region of Enrollment United States | 116 participants | 46 participants | 41 participants | 5 participants | 2 participants | 1 participants | 21 participants |
| Sex: Female, Male Female | 50 Participants | 21 Participants | 17 Participants | 2 Participants | 1 Participants | 1 Participants | 8 Participants |
| Sex: Female, Male Male | 66 Participants | 25 Participants | 24 Participants | 3 Participants | 1 Participants | 0 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 46 | 0 / 41 | 0 / 5 | 0 / 2 | 0 / 1 | 0 / 0 | 0 / 21 |
| serious Total, serious adverse events | 10 / 46 | 10 / 41 | 2 / 5 | 1 / 2 | 0 / 1 | 0 / 0 | 0 / 21 |
Outcome results
Primary
Number of Participants Who Experience Optimal Imaging in Adult and Pediatric Brain Tumors to Establish Timing and Sequencing Parameters 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.
Time frame: 24 hours (some patients between 3 and 72 hours) after administration of Combidex
Population: No eligible participants were identified to enroll in Group 6. Data not collected for Group 3 due to early study termination.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combidex Only (Group 1) | Number of Participants Who Experience Optimal Imaging in Adult and Pediatric Brain Tumors to Establish Timing and Sequencing Parameters of Combidex. | 36 Participants |
| Combidex and Neurosurgery (Group 2) | Number of Participants Who Experience Optimal Imaging in Adult and Pediatric Brain Tumors to Establish Timing and Sequencing Parameters of Combidex. | 35 Participants |
| Combidex Only (Group 4) | Number of Participants Who Experience Optimal Imaging in Adult and Pediatric Brain Tumors to Establish Timing and Sequencing Parameters of Combidex. | 2 Participants |
| Combidex and Neurosurgery (Group 5) | Number of Participants Who Experience Optimal Imaging in Adult and Pediatric Brain Tumors to Establish Timing and Sequencing Parameters of Combidex. | 1 Participants |
| Inflammatory Lesions (Group 7) | Number of Participants Who Experience Optimal Imaging in Adult and Pediatric Brain Tumors to Establish Timing and Sequencing Parameters of Combidex. | 20 Participants |
Secondary
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
Population: Data was not collected due to early study termination (Combidex became obsolete with introduction of ferumoxytol and this study was closed early).
Secondary
Compare Combidex Imaging in Brain Tumor Patients, With Other CNS Inflammatory Lesions Such as Multiple Sclerosis and Stroke.
Time frame: 2 years
Population: Data was not collected due to early study termination (Combidex became obsolete with introduction of ferumoxytol and this study was closed early).
Secondary
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
Population: Data was not collected due to early study termination (Combidex became obsolete with introduction of ferumoxytol and this study was closed early).