Trial Outcomes & Findings for Ferumoxytol in Improving MR Imaging in Patients With High-Grade Brain Tumors or Cerebral Metastases (NCT NCT00103038)
NCT ID: NCT00103038
Last Updated: 2022-06-09
Results Overview
Appropriate descriptive statistics (mean, standard deviation, minimum, median, and maximum) will be estimated for the imaging parameters Ktrans. Frequency distributions of each parameter will also be described to assess normality. Pearson's correlation coefficients will be estimated to describe potential relationships among these various measures.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
155 participants
Primary outcome timeframe
Assessed after each visit for up to 6 imaging sessions (up to 5 years)
Results posted on
2022-06-09
Participant Flow
Participant milestones
| Measure |
Malignant Brain Tumor Patients Undergoing Brain MRI (With Both Ferumoxytol and Gadolinium)
Study patients: adult patients with high grade primary malignant brain tumors or with known or suspected brain metastases from histologically confirmed primary cancer
Study procedures: patients will receive IV ferumoxytol (maximum dose 4 mg/kg, over at least 15 minutes) beginning approximately 15 seconds after start of 3T DSC-MRI and GBCA IV approximately 1 minute and 50 seconds after start of 3T DCE-MRI on day 1. Patients will also undergo MRI without contrast at baseline (before and on day 2. Imaging with ferumoxytol, GBCA and without contrast repeats every 3 weeks for a total of 6 more imaging sessions over up to 5 years.
3 Tesla Magnetic Resonance Imaging: Undergo 3T MRI
Dynamic Contrast-Enhanced Magnetic Resonance Imaging: Undergo 3T DCE-MRI
Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging: Undergo 3T DSC-MRI
Ferumoxytol: Given IV
Gadolinium: Given IV
MRI-Based Angiogram: Undergo MRA
|
|---|---|
|
Overall Study
STARTED
|
155
|
|
Overall Study
COMPLETED
|
142
|
|
Overall Study
NOT COMPLETED
|
13
|
Reasons for withdrawal
| Measure |
Malignant Brain Tumor Patients Undergoing Brain MRI (With Both Ferumoxytol and Gadolinium)
Study patients: adult patients with high grade primary malignant brain tumors or with known or suspected brain metastases from histologically confirmed primary cancer
Study procedures: patients will receive IV ferumoxytol (maximum dose 4 mg/kg, over at least 15 minutes) beginning approximately 15 seconds after start of 3T DSC-MRI and GBCA IV approximately 1 minute and 50 seconds after start of 3T DCE-MRI on day 1. Patients will also undergo MRI without contrast at baseline (before and on day 2. Imaging with ferumoxytol, GBCA and without contrast repeats every 3 weeks for a total of 6 more imaging sessions over up to 5 years.
3 Tesla Magnetic Resonance Imaging: Undergo 3T MRI
Dynamic Contrast-Enhanced Magnetic Resonance Imaging: Undergo 3T DCE-MRI
Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging: Undergo 3T DSC-MRI
Ferumoxytol: Given IV
Gadolinium: Given IV
MRI-Based Angiogram: Undergo MRA
|
|---|---|
|
Overall Study
Withdrawal by Subject
|
8
|
|
Overall Study
Screen failure
|
3
|
|
Overall Study
Death
|
1
|
|
Overall Study
Physician Decision
|
1
|
Baseline Characteristics
Ferumoxytol in Improving MR Imaging in Patients With High-Grade Brain Tumors or Cerebral Metastases
Baseline characteristics by cohort
| Measure |
Malignant Brain Tumor Patients Undergoing Brain MRI (With Both Ferumoxytol and Gadolinium)
n=155 Participants
Study patients: adult patients with high grade primary malignant brain tumors or with known or suspected brain metastases from histologically confirmed primary cancer
Study procedures: patients will receive IV ferumoxytol (maximum dose 4 mg/kg, over at least 15 minutes) beginning approximately 15 seconds after start of 3T DSC-MRI and GBCA IV approximately 1 minute and 50 seconds after start of 3T DCE-MRI on day 1. Patients will also undergo MRI without contrast at baseline (before and on day 2. Imaging with ferumoxytol, GBCA and without contrast repeats every 3 weeks for a total of 6 more imaging sessions over up to 5 years.
3 Tesla Magnetic Resonance Imaging: Undergo 3T MRI
Dynamic Contrast-Enhanced Magnetic Resonance Imaging: Undergo 3T DCE-MRI
Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging: Undergo 3T DSC-MRI
Ferumoxytol: Given IV
Gadolinium: Given IV
MRI-Based Angiogram: Undergo MRA
|
|---|---|
|
Age, Continuous
|
51.71 years
STANDARD_DEVIATION 13.81 • n=5 Participants
|
|
Sex: Female, Male
Female
|
70 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
85 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
150 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
147 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
|
Type of brain malignancy
Glioblastoma
|
67 Participants
n=5 Participants
|
|
Type of brain malignancy
Anaplastic Astrocytoma
|
19 Participants
n=5 Participants
|
|
Type of brain malignancy
Anaplastic Oligodendroglioma
|
19 Participants
n=5 Participants
|
|
Type of brain malignancy
Primary CNS Lymphoma
|
4 Participants
n=5 Participants
|
|
Type of brain malignancy
Brain metastasis
|
18 Participants
n=5 Participants
|
|
Type of brain malignancy
Other
|
17 Participants
n=5 Participants
|
|
Type of brain malignancy
Unknown
|
11 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Assessed after each visit for up to 6 imaging sessions (up to 5 years)Population: Software to derive K trans values from acquired images is not available and enhancement comparison between gadolinium and ferumoxytol K trans values is not possible to date.
Appropriate descriptive statistics (mean, standard deviation, minimum, median, and maximum) will be estimated for the imaging parameters Ktrans. Frequency distributions of each parameter will also be described to assess normality. Pearson's correlation coefficients will be estimated to describe potential relationships among these various measures.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Summarized after completion of up to 6 imaging sessions (up to 5 years)Compare rCBV measurements in regions of interest obtained from ferumoxytol DSC-MRI with gadolinium based contrast agent (GBCA) MR images to evaluate vascular properties of brain tumors. CBV maps were generated by applying tracer kinetic model to the first pass of the contrast bolus. Voxelwise CBV maps were coregistered to T1 weighted images and then normalized by dividing by the mean of normal appearing white matter CBV in the same region in the contralateral hemisphere. RCBV values (as the area under the signal intensity curve, normalized by the area under the curve for the control region) were obtained. Values range from 0 (low intensity) to 180 (highest intensity).
Outcome measures
| Measure |
Malignant Brain Tumor Patients Undergoing Brain MRI (With Both Ferumoxytol and Gadolinium)
n=12 Participants
Study patients: adult patients with high grade primary malignant brain tumors or with known or suspected brain metastases from histologically confirmed primary cancer
Study procedures: patients will receive IV ferumoxytol (maximum dose 4 mg/kg, over at least 15 minutes) beginning approximately 15 seconds after start of 3T DSC-MRI and GBCA IV approximately 1 minute and 50 seconds after start of 3T DCE-MRI on day 1. Patients will also undergo MRI without contrast at baseline (before and on day 2. Imaging with ferumoxytol, GBCA and without contrast repeats every 3 weeks for a total of 6 more imaging sessions over up to 5 years.
3 Tesla Magnetic Resonance Imaging: Undergo 3T MRI
Dynamic Contrast-Enhanced Magnetic Resonance Imaging: Undergo 3T DCE-MRI
Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging: Undergo 3T DSC-MRI
Ferumoxytol: Given IV
Gadolinium: Given IV
MRI-Based Angiogram: Undergo MRA
|
Malignant Brain Tumor Patients Undergoing Brain- Ferumoxytol-enhanced MRI
Study patients: adult patients with high grade primary malignant brain tumors or with known or suspected brain metastases from histologically confirmed primary cancer
Study procedures: patients will receive IV ferumoxytol (maximum dose 4 mg/kg, over at least 15 minutes) beginning approximately 15 seconds after start of 3T DSC-MRI and GBCA IV approximately 1 minute and 50 seconds after start of 3T DCE-MRI on day 1. Patients will also undergo MRI without contrast at baseline (before and on day 2. Imaging with ferumoxytol, GBCA and without contrast repeats every 3 weeks for a total of 6 more imaging sessions over up to 5 years.
3 Tesla Magnetic Resonance Imaging: Undergo 3T MRI
Dynamic Contrast-Enhanced Magnetic Resonance Imaging: Undergo 3T DCE-MRI
Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging: Undergo 3T DSC-MRI
Ferumoxytol: Given IV
Gadolinium: Given IV
MRI-Based Angiogram: Undergo MRA
|
|---|---|---|
|
Utility of Ferumoxytol and Gadolinium Based Contrast Agents for Improved Imaging Biomarkers of Malignant Brain Tumors in a Single Imaging Session by Comparing Dynamic Susceptibility Contrast (DSC) Determined Relative Cerebral Blood Volume (rCBV) Maps.
Tumor area gadolinium rCBV
|
39 Values on a scale
Interval 0.0 to 180.0
|
—
|
|
Utility of Ferumoxytol and Gadolinium Based Contrast Agents for Improved Imaging Biomarkers of Malignant Brain Tumors in a Single Imaging Session by Comparing Dynamic Susceptibility Contrast (DSC) Determined Relative Cerebral Blood Volume (rCBV) Maps.
Peritumor area ferumoxytol rCBV
|
136 Values on a scale
Interval 0.0 to 180.0
|
—
|
|
Utility of Ferumoxytol and Gadolinium Based Contrast Agents for Improved Imaging Biomarkers of Malignant Brain Tumors in a Single Imaging Session by Comparing Dynamic Susceptibility Contrast (DSC) Determined Relative Cerebral Blood Volume (rCBV) Maps.
Peritumor area gadolinium rCBV
|
146 Values on a scale
Interval 0.0 to 180.0
|
—
|
|
Utility of Ferumoxytol and Gadolinium Based Contrast Agents for Improved Imaging Biomarkers of Malignant Brain Tumors in a Single Imaging Session by Comparing Dynamic Susceptibility Contrast (DSC) Determined Relative Cerebral Blood Volume (rCBV) Maps.
Tumor area ferumoxytol rCBV
|
54 Values on a scale
Interval 0.0 to 180.0
|
—
|
SECONDARY outcome
Timeframe: Summarized after completion of up to 6 imaging sessions (up to 5 years)Population: 58 participants had both appropriate ferumoxytol and gadolinium scans available for analysis for this outcome.
We analyzed 193 sets of post-gadoteriol and 24 hours post-ferumoxytol T1 weighted scans from 58 patient with high grade glioma. Enhancement volumes normalized to normal appearing white matter were calculated with histogram analysis. Enhancement cube root volumes were compared between the two contrast agents. Ferumoxytol and gadolinium enhanced MR images were obtained from each participant.
Outcome measures
| Measure |
Malignant Brain Tumor Patients Undergoing Brain MRI (With Both Ferumoxytol and Gadolinium)
n=193 MR images/scans
Study patients: adult patients with high grade primary malignant brain tumors or with known or suspected brain metastases from histologically confirmed primary cancer
Study procedures: patients will receive IV ferumoxytol (maximum dose 4 mg/kg, over at least 15 minutes) beginning approximately 15 seconds after start of 3T DSC-MRI and GBCA IV approximately 1 minute and 50 seconds after start of 3T DCE-MRI on day 1. Patients will also undergo MRI without contrast at baseline (before and on day 2. Imaging with ferumoxytol, GBCA and without contrast repeats every 3 weeks for a total of 6 more imaging sessions over up to 5 years.
3 Tesla Magnetic Resonance Imaging: Undergo 3T MRI
Dynamic Contrast-Enhanced Magnetic Resonance Imaging: Undergo 3T DCE-MRI
Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging: Undergo 3T DSC-MRI
Ferumoxytol: Given IV
Gadolinium: Given IV
MRI-Based Angiogram: Undergo MRA
|
Malignant Brain Tumor Patients Undergoing Brain- Ferumoxytol-enhanced MRI
n=193 MR images/scans
Study patients: adult patients with high grade primary malignant brain tumors or with known or suspected brain metastases from histologically confirmed primary cancer
Study procedures: patients will receive IV ferumoxytol (maximum dose 4 mg/kg, over at least 15 minutes) beginning approximately 15 seconds after start of 3T DSC-MRI and GBCA IV approximately 1 minute and 50 seconds after start of 3T DCE-MRI on day 1. Patients will also undergo MRI without contrast at baseline (before and on day 2. Imaging with ferumoxytol, GBCA and without contrast repeats every 3 weeks for a total of 6 more imaging sessions over up to 5 years.
3 Tesla Magnetic Resonance Imaging: Undergo 3T MRI
Dynamic Contrast-Enhanced Magnetic Resonance Imaging: Undergo 3T DCE-MRI
Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging: Undergo 3T DSC-MRI
Ferumoxytol: Given IV
Gadolinium: Given IV
MRI-Based Angiogram: Undergo MRA
|
|---|---|---|
|
Compare Number and Size of Tumors Imaged With Ferumoxytol and Gadolinium Based Contrast Agents (Cube Root Volume)
|
21.71 mm
Standard Deviation 6.396
|
18.71 mm
Standard Deviation 6.884
|
SECONDARY outcome
Timeframe: Summarized after completion of up to 6 imaging sessions (up to 5 years)Population: 58 participants had both appropriate ferumoxytol and gadolinium scans available for analysis for this outcome.
We analyzed 193 sets of post-gadoteriol and 24 hours post-ferumoxytol T1 weighted scans from 58 patient with high grade glioma. Signal intensities normalized to normal appearing white matter were calculated with histogram analysis. Signal intensities were compared between the two contrast agents. Ferumoxytol and gadolinium enhanced MR images were obtained from each participant. Signal intensities were normalized to the signal intensity value of non-enhancing voxels inside the manual ROI (the relative complement of the final mask in Q, i.e. Q \\ \[A ∩ B ∩ C\]). Higher values in signal intensity indicated increased image enhancement.
Outcome measures
| Measure |
Malignant Brain Tumor Patients Undergoing Brain MRI (With Both Ferumoxytol and Gadolinium)
n=193 Images
Study patients: adult patients with high grade primary malignant brain tumors or with known or suspected brain metastases from histologically confirmed primary cancer
Study procedures: patients will receive IV ferumoxytol (maximum dose 4 mg/kg, over at least 15 minutes) beginning approximately 15 seconds after start of 3T DSC-MRI and GBCA IV approximately 1 minute and 50 seconds after start of 3T DCE-MRI on day 1. Patients will also undergo MRI without contrast at baseline (before and on day 2. Imaging with ferumoxytol, GBCA and without contrast repeats every 3 weeks for a total of 6 more imaging sessions over up to 5 years.
3 Tesla Magnetic Resonance Imaging: Undergo 3T MRI
Dynamic Contrast-Enhanced Magnetic Resonance Imaging: Undergo 3T DCE-MRI
Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging: Undergo 3T DSC-MRI
Ferumoxytol: Given IV
Gadolinium: Given IV
MRI-Based Angiogram: Undergo MRA
|
Malignant Brain Tumor Patients Undergoing Brain- Ferumoxytol-enhanced MRI
n=58 Participants
Study patients: adult patients with high grade primary malignant brain tumors or with known or suspected brain metastases from histologically confirmed primary cancer
Study procedures: patients will receive IV ferumoxytol (maximum dose 4 mg/kg, over at least 15 minutes) beginning approximately 15 seconds after start of 3T DSC-MRI and GBCA IV approximately 1 minute and 50 seconds after start of 3T DCE-MRI on day 1. Patients will also undergo MRI without contrast at baseline (before and on day 2. Imaging with ferumoxytol, GBCA and without contrast repeats every 3 weeks for a total of 6 more imaging sessions over up to 5 years.
3 Tesla Magnetic Resonance Imaging: Undergo 3T MRI
Dynamic Contrast-Enhanced Magnetic Resonance Imaging: Undergo 3T DCE-MRI
Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging: Undergo 3T DSC-MRI
Ferumoxytol: Given IV
Gadolinium: Given IV
MRI-Based Angiogram: Undergo MRA
|
|---|---|---|
|
Compare Number and Size of Tumors Imaged With Ferumoxytol and Gadolinium Based Contrast Agents (Signal Intensity)
|
1.36 ratio
Standard Deviation 0.107
|
1.26 ratio
Standard Deviation 0.108
|
SECONDARY outcome
Timeframe: Assessed after each visit for up to 6 imaging sessions (up to 5 years)Population: 68 participants had appropriate ferumoxytol scans available for analysis for this outcome.
We evaluated overall survival in patients with pseudopregression or real tumor progression by using relative cerebral blood volume values on ferumoxytol enhanced perfusion MRIs.
Outcome measures
| Measure |
Malignant Brain Tumor Patients Undergoing Brain MRI (With Both Ferumoxytol and Gadolinium)
n=68 Participants
Study patients: adult patients with high grade primary malignant brain tumors or with known or suspected brain metastases from histologically confirmed primary cancer
Study procedures: patients will receive IV ferumoxytol (maximum dose 4 mg/kg, over at least 15 minutes) beginning approximately 15 seconds after start of 3T DSC-MRI and GBCA IV approximately 1 minute and 50 seconds after start of 3T DCE-MRI on day 1. Patients will also undergo MRI without contrast at baseline (before and on day 2. Imaging with ferumoxytol, GBCA and without contrast repeats every 3 weeks for a total of 6 more imaging sessions over up to 5 years.
3 Tesla Magnetic Resonance Imaging: Undergo 3T MRI
Dynamic Contrast-Enhanced Magnetic Resonance Imaging: Undergo 3T DCE-MRI
Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging: Undergo 3T DSC-MRI
Ferumoxytol: Given IV
Gadolinium: Given IV
MRI-Based Angiogram: Undergo MRA
|
Malignant Brain Tumor Patients Undergoing Brain- Ferumoxytol-enhanced MRI
Study patients: adult patients with high grade primary malignant brain tumors or with known or suspected brain metastases from histologically confirmed primary cancer
Study procedures: patients will receive IV ferumoxytol (maximum dose 4 mg/kg, over at least 15 minutes) beginning approximately 15 seconds after start of 3T DSC-MRI and GBCA IV approximately 1 minute and 50 seconds after start of 3T DCE-MRI on day 1. Patients will also undergo MRI without contrast at baseline (before and on day 2. Imaging with ferumoxytol, GBCA and without contrast repeats every 3 weeks for a total of 6 more imaging sessions over up to 5 years.
3 Tesla Magnetic Resonance Imaging: Undergo 3T MRI
Dynamic Contrast-Enhanced Magnetic Resonance Imaging: Undergo 3T DCE-MRI
Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging: Undergo 3T DSC-MRI
Ferumoxytol: Given IV
Gadolinium: Given IV
MRI-Based Angiogram: Undergo MRA
|
|---|---|---|
|
Overall Survival in Participants With Pseudoprogression With or Real Tumor Progression Using Ferumoxytol Enchanced Perfusion MRI
Median survival in patients with pseudoprogression seen on Fe-MRI
|
34.7 months
Interval 20.3 to 54.1
|
—
|
|
Overall Survival in Participants With Pseudoprogression With or Real Tumor Progression Using Ferumoxytol Enchanced Perfusion MRI
Median survival in patients with real progression seen on Fe-MRI
|
13.4 months
Interval 11.1 to 19.5
|
—
|
Adverse Events
Malignant Brain Tumor Patients Undergoing Brain MRI (With Both Ferumoxytol and Gadolinium)
Serious events: 0 serious events
Other events: 12 other events
Deaths: 119 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Malignant Brain Tumor Patients Undergoing Brain MRI (With Both Ferumoxytol and Gadolinium)
n=152 participants at risk
Study patients: adult patients with high grade primary malignant brain tumors
Study procedures: patients will receive IV ferumoxytol (maximum dose 4 mg/kg, over at least 15 minutes) beginning approximately 15 seconds after start of 3T DSC-MRI and GBCA IV approximately 1 minute and 50 seconds after start of 3T DCE-MRI on day 1. Patients will also undergo MRI without contrast at baseline (before and on day 2. Imaging with ferumoxytol, GBCA and without contrast repeats every 3 weeks for a total of 6 more imaging sessions over up to 5 years.
3 Tesla Magnetic Resonance Imaging: Undergo 3T MRI
Dynamic Contrast-Enhanced Magnetic Resonance Imaging: Undergo 3T DCE-MRI
Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging: Undergo 3T DSC-MRI
Ferumoxytol: Given IV
Gadolinium: Given IV
MRI-Based Angiogram: Undergo MRA
|
|---|---|
|
Cardiac disorders
Hypertension
|
7.9%
12/152 • Number of events 14 • Subjects were evaluated for adverse events approximately 4-6 weeks after each study visit, up to 5 years.
Patients are monitored for adverse events in the scanning unit for the entire MRI time and 30 minutes after the final infusion of ferumoxytol An additional phone follow up visit was performed 4-6 weeks after each imaging session to focus on any new adverse events
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place