Trial Outcomes & Findings for Ferumoxytol- and Gadolinium-Labeled MRI in Measuring Tumors Before or After Treatment in Patients With Primary or Metastatic Brain Tumors (NCT NCT00659126)

Last Updated: 2023-09-07

Results Overview

Paired sample t-tests will be used for primary descriptive comparisons. Secondary analyses will use a repeated measures analysis of variance (ANOVA) model to compare 3T and 7T while adjusting for other factors including tumor type, prior therapy, and, potentially, important baseline factors that differ between the subjects assigned to the two field strengths. Normality will be assessed graphically and, if needed, a transformation (e.g. the logarithmic transform) will be applied.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

40 participants

Primary outcome timeframe

Baseline to day 1

Results posted on

2023-09-07

Participant Flow

Participant milestones

Participant milestones
Measure	Gadolinium and Ferumoxytol Magnetic Resonance Imaging at 3 Tesla in Subjects With Brain Tumors A subset of subjects with primary or metastatic brain tumors will be assigned to 3 Tesla MRI and will undergo gadolinium enhanced imaging on day 1, ferumoxytol enhanced imaging on day 2, and a non contrast ("post-ferumoxytol") imaging on day 3. All scans will be performed on a 3 Tesla MRI scanner.	Gadolinium and Ferumoxytol Magnetic Resonance Imaging at 7 Tesla in Subjects With Brain Tumors A subset of subjects with primary or metastatic brain tumors will be assigned to 7 Tesla MRI and will undergo gadolinium enhanced imaging on day 1, ferumoxytol enhanced imaging on day 2, and a non contrast ("post-ferumoxytol") imaging on day 3. All scans will be performed on a 7 Tesla MRI scanner.
Overall Study STARTED	15	25
Overall Study COMPLETED	12	21
Overall Study NOT COMPLETED	3	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Gadolinium and Ferumoxytol Magnetic Resonance Imaging at 3 Tesla in Subjects With Brain Tumors A subset of subjects with primary or metastatic brain tumors will be assigned to 3 Tesla MRI and will undergo gadolinium enhanced imaging on day 1, ferumoxytol enhanced imaging on day 2, and a non contrast ("post-ferumoxytol") imaging on day 3. All scans will be performed on a 3 Tesla MRI scanner.	Gadolinium and Ferumoxytol Magnetic Resonance Imaging at 7 Tesla in Subjects With Brain Tumors A subset of subjects with primary or metastatic brain tumors will be assigned to 7 Tesla MRI and will undergo gadolinium enhanced imaging on day 1, ferumoxytol enhanced imaging on day 2, and a non contrast ("post-ferumoxytol") imaging on day 3. All scans will be performed on a 7 Tesla MRI scanner.
Overall Study Adverse Event	2	2
Overall Study Screen failure	1	1
Overall Study Technical problems with MRI	0	1

Baseline Characteristics

Ferumoxytol- and Gadolinium-Labeled MRI in Measuring Tumors Before or After Treatment in Patients With Primary or Metastatic Brain Tumors

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Gadolinium and Ferumoxytol Magnetic Resonance Imaging at 3 Tesla in Subjects With Brain Tumors n=15 Participants A subset of subjects with primary or metastatic brain tumors will be assigned to 3 Tesla MRI and will undergo gadolinium enhanced imaging on day 1, ferumoxytol enhanced imaging on day 2, and a non contrast ("post-ferumoxytol") imaging on day 3. All scans will be performed on a 3 Tesla MRI scanner.	Gadolinium and Ferumoxytol Magnetic Resonance Imaging at 7 Tesla in Subjects With Brain Tumors n=25 Participants A subset of subjects with primary or metastatic brain tumors will be assigned to 7 Tesla MRI and will undergo gadolinium enhanced imaging on day 1, ferumoxytol enhanced imaging on day 2, and a non contrast ("post-ferumoxytol") imaging on day 3. All scans will be performed on a 7 Tesla MRI scanner.	Total n=40 Participants Total of all reporting groups
Age, Continuous	55 years STANDARD_DEVIATION 12.91 • n=5 Participants	52.52 years STANDARD_DEVIATION 13.69 • n=7 Participants	53.45 years STANDARD_DEVIATION 13.29 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	10 Participants n=7 Participants	14 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	15 Participants n=7 Participants	26 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	13 Participants n=5 Participants	24 Participants n=7 Participants	37 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	14 Participants n=5 Participants	25 Participants n=7 Participants	39 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Brain tumor type Glioblastoma	8 Participants n=5 Participants	8 Participants n=7 Participants	16 Participants n=5 Participants
Brain tumor type Anaplastic astrocytoma	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Brain tumor type Astrocytoma grade II	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Brain tumor type Anaplastic oligodendroglioma	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Brain tumor type Oligodendroglioma grade II	0 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants
Brain tumor type Meningioma	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Brain tumor type Metastasis	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Brain tumor type CNS lymphoma	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Brain tumor type Other	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to day 1

Population: The first primary objective was to use dynamic contrast enhancement (DCE) MRI. Due to limitations of the scanners, these images were not collected. Dynamic susceptibility contrast (DSC) images were collected which are reported in the second primary objective.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Day 1 to day 2

Population: Other patients were excluded due to poor DSC graph or no residual tumor for measurement or residual tumor stayed within vascular lumen. Non-contrast (day 3) data not collected.

A two sample t-test was used for primary descriptive comparisons since CNR was measured on different subjects at 3T and 7T. There were no repeated measures in the resulting data. Given the small sample size, a linear regression was conducted to compare CNR between 3T and 7T only adjusted for Fe dose. No other adjusted analyses were conducted. CNR was compared between 3T and 7T for both Ferumoxytol and Gadolinum. Ferumoxytol was administered using three injections and CNR was measured after each injection, thus we have three measures of CNR (Fe1CNR, Fe2CNR and Fe3CNR).

Outcome measures

Outcome measures
Measure	Gadolinium and Ferumoxytol Magnetic Resonance Imaging at 3 Tesla in Subjects With Brain Tumors n=10 Participants A subset of subjects with primary or metastatic brain tumors will be assigned to 3 Tesla MRI and will undergo gadolinium enhanced imaging on day 1, ferumoxytol enhanced imaging on day 2, and a non contrast ("post-ferumoxytol") imaging on day 3. All scans will be performed on a 3 Tesla MRI scanner.	Gadolinium and Ferumoxytol Magnetic Resonance Imaging at 7 Tesla in Subjects With Brain Tumors n=10 Participants A subset of subjects with primary or metastatic brain tumors will be assigned to 7 Tesla MRI and will undergo gadolinium enhanced imaging on day 1, ferumoxytol enhanced imaging on day 2, and a non contrast ("post-ferumoxytol") imaging on day 3. All scans will be performed on a 7 Tesla MRI scanner.
CNR, in Terms of Normalized Signal Intensity Changes, for Dynamic Susceptibility Contrast (DSC) MRI Data Sets at 3T and 7T (Gadolinium and Ferumoxytol) Gadolinium	1.34 ratio Standard Deviation .923	.912 ratio Standard Deviation .519
CNR, in Terms of Normalized Signal Intensity Changes, for Dynamic Susceptibility Contrast (DSC) MRI Data Sets at 3T and 7T (Gadolinium and Ferumoxytol) Ferumoxytol 1st dose	1.034 ratio Standard Deviation .611	.669 ratio Standard Deviation .644
CNR, in Terms of Normalized Signal Intensity Changes, for Dynamic Susceptibility Contrast (DSC) MRI Data Sets at 3T and 7T (Gadolinium and Ferumoxytol) Ferumoxytol 2nd dose	1.27 ratio Standard Deviation .886	1.08 ratio Standard Deviation 1.15
CNR, in Terms of Normalized Signal Intensity Changes, for Dynamic Susceptibility Contrast (DSC) MRI Data Sets at 3T and 7T (Gadolinium and Ferumoxytol) Ferumoxytol 3rd dose	1.45 ratio Standard Deviation .893	.886 ratio Standard Deviation .964

SECONDARY outcome

Timeframe: Day 1 to day 2

Population: Data for secondary outcomes were not collected. The study was terminated early as the 7t scanner was not providing the images needed, and we did not have the funding to continue.

Mixed model repeated measures ANOVAs will be fit. Factors will include imaging agent (Gd or ferumoxytol) and field strength (3T and 7T). Each subject will contribute one measure for each combination of imaging agent and field strength (4 measures total).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 1 to day 2

Population: Data for secondary outcomes were not collected. The study was terminated early as the 7t scanner was not providing the images needed, and we did not have the funding to continue.

Blood volumes will be compared using repeated measures ANOVA to compare the imaging agents.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 1 to day 2

Population: Data for secondary outcomes were not collected. The study was terminated early as the 7t scanner was not providing the images needed, and we did not have the funding to continue.

Analysis will also include covariates of prior therapy. For the comparisons between treated and untreated subjects, means and confidence intervals will be estimated for each group for the perfusion and permeability measures and for the baseline characteristics.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At time of surgery

Population: Data for secondary outcomes were not collected. The study was terminated early as the 7t scanner was not providing the images needed, and we did not have the funding to continue.

The pathology will be analyzed qualitatively for the presence of iron staining. The amount and localization of the staining will be assessed, with attention paid to whether the tumor cells themselves or reactive cells in and around the tumor demonstrate iron uptake.

Outcome measures

Outcome data not reported

Adverse Events

Gadolinium and Ferumoxytol Magnetic Resonance Imaging at 3 Tesla in Subjects With Brain Tumors

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Gadolinium and Ferumoxytol Magnetic Resonance Imaging at 7 Tesla in Subjects With Brain Tumors

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Gadolinium and Ferumoxytol Magnetic Resonance Imaging at 3 Tesla in Subjects With Brain Tumors n=12 participants at risk A subset of subjects with primary or metastatic brain tumors will be assigned to 3 Tesla MRI and will undergo gadolinium enhanced imaging on day 1, ferumoxytol enhanced imaging on day 2, and a non contrast ("post-ferumoxytol") imaging on day 3. All scans will be performed on a 3 Tesla MRI scanner.	Gadolinium and Ferumoxytol Magnetic Resonance Imaging at 7 Tesla in Subjects With Brain Tumors n=21 participants at risk A subset of subjects with primary or metastatic brain tumors will be assigned to 7 Tesla MRI and will undergo gadolinium enhanced imaging on day 1, ferumoxytol enhanced imaging on day 2, and a non contrast ("post-ferumoxytol") imaging on day 3. All scans will be performed on a 7 Tesla MRI scanner.
Gastrointestinal disorders Diarrhea	0.00% 0/12 • Subjects were monitored for adverse events from day 1 of imaging session to 4 to 6 weeks after completing imaging. Non-contrast (day 3) data not collected.	4.8% 1/21 • Number of events 1 • Subjects were monitored for adverse events from day 1 of imaging session to 4 to 6 weeks after completing imaging. Non-contrast (day 3) data not collected.

Additional Information

Amy Huddleston

Oregon Health and Science University

Phone: 5034945626

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place