A Phase 2 interventional study of ¹⁸F-Fluoromisonidazole and Computed Tomography in IDH Wild Type Glioblastoma, sponsored by OHSU Knight Cancer Institute. Recruiting at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-18.
Sponsored by OHSU Knight Cancer Institute · Phase 2, Interventional, and Diagnostic
This phase II trial studies how well 18F- fluoromisonidazole (FMISO) works with positron emission tomography (PET)/magnetic resonance imaging (MRI) in assessing participants with malignant (cancerous) brain tumors. Two contrast agents called gadolinium and ferumoxytol are used during some of the MRI scans. A contrast agent is a liquid-like dye that is given intravenously (IV) to help imaging machines create pictures. The study drug, called FMISO, provides information about the oxygen levels in a tumor, which may affect how the tumor behaves. PET/MRI imaging produces images of the brain and how the body functions. FMISO PET/MRI may help investigators see how much oxygen is getting in the brain tumors.
PRIMARY OBJECTIVES:
I. Determine the feasibility of obtaining 18F-fluoromisonidazole (FMISO) PET (hypoxic volume and tumor to blood background values [T/B]) and dynamic susceptibility contrast enhanced (DSC), diffusion-weighted imaging (DWI), \& segregation \& extravascular localization of ferumoxytol imaging (SELFI) MRI measures in patients with intracranial brain tumors.
II. Determine if MRI contrast-enhancement and hypoxic volume are imaging profiles of glioblastoma immunotherapy-mediated pseudoprogression or true progression in a clinical trial.
III. Determine if SELFI hypoxic fraction are imaging biomarkers of glioblastoma neuroinflammation.
SECONDARY OBJECTIVES:
I. Determine the feasibility of baseline and follow-up ferumoxytol (Fe)-enhanced FMISO PET and MR imaging co-registration.
II. Assess diagnostic performance of imaging metrics to identify failed therapy at earlier imaging timepoints before presumed progression.
III. Determine the reliability of the pre-therapy FMISO PET imaging metrics as assessed by baseline "test" and "retest experiments.
IV. Compare the diagnostic performance of SELFI hypoxic fraction to Modified Response Assessment in Neuro-Oncology (mRANO) criteria.
V. Determine the sensitivity and specificity of SELFI hypoxic fraction for the diagnosis of neuroinflammation and recurrent disease.
VI. Assess progression free survival. VII. Assess overall survival. VIII. Determine change in imaging metrics from post-therapy and disease progression in differentiating neuroinflammation from recurrent disease.
IX. Determine optimal SELFI hypoxic fraction imaging parameters. X. Correlate SELFI hypoxic fraction with innate immune phenotype and hypoxia expression.
TERTIARY OBJECTIVE:
I. Determine the reproducibility of the baseline FMISO PET imaging metrics as assessed by baseline "test" and "retest" experiments.
OUTLINE:
Participants receive FMISO and/or FE IV. Patients also undergo dynamic PET/computed tomography (CT) or PET/MRI over 120 minutes beginning 1 minute prior to FMISO injection, and static PET/CT or PET/MRI over 20-40 minutes approximately 90 minutes after FMISO injection. Participants may then receive FMISO and/or Fe IV and gadolinium IV and undergo PET/MRI scan, followed by an additional PET/MRI scan without FMISO and/or Fe and gadolinium the following day. These scans may repeat every 4 weeks up to 4 times. Supplemental oxygen may be administered to affect MRI signal change.
After conclusion of the diagnostic tests, participants are followed for up to 5 years.
Exclusion Criteria:
Participants receive FMISO and/or FE IV. Patients also undergo dynamic PET/CT or PET/MRI over 120 minutes beginning 1 minute prior to FMISO injection, and static PET/CT or PET/MRI over 20-40 minutes approximately 90 minutes after FMISO injection. Participants may then receive FMISO and/or Fe IV and gadolinium IV and undergo PET/MRI scan, followed by an additional PET/MRI scan without FMISO and/or Fe and gadolinium the following day. These scans may repeat every 4 weeks up to 4 times. Supplemental oxygen may be administered to affect MRI signal change.
Drug: ¹⁸F-Fluoromisonidazole · Procedure: Computed Tomography · Procedure: Magnetic Resonance Imaging · Procedure: Positron Emission Tomography · Procedure: Oxygen Therapy · Drug: Ferumoxytol · Drug: Gadolinium
Given IV
Also known as: ¹⁸F-MISO, ¹⁸F-Misonidazole, FMISO
Undergo PET/CT
Also known as: CAT, CAT Scan, Computerized Axial Tomography, Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography
Undergo PET/MRI or PET/CT
Also known as: Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR Imaging, MRI, MRI Scan, NMR Imaging, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), NMRI, Nuclear Magnetic Resonance Imaging
Undergo PET/MRI
Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging
Receive supplemental oxygen
Also known as: supplemental oxygen therapy
Given IV
Also known as: Feraheme, Ferumoxytol, ferumoxytol, FERUMOXYTOL NON-STOICHIOMETRIC MAGNETITE, Ferumoxytol Non-Stoichiometric Magnetite
Given IV
Successful production of images
Assessed as a factor of generating quantitative positron emission tomography (PET)/magnetic resonance imaging (MRI) metrics (intra-tumoral FMISO tumor to blood \[T/B\] level, hypoxic volume, dynamic susceptibility contrast enhanced \[DSC\], diffusion-weighted imaging \[DWI\], and segregation \& extravascular localization of ferumoxytol imaging \[SELFI\] values, and tissue oxygen maps). Images generated during the administration of oxygen will be used to generate tissue oxygen maps of the brain. Following completion of cohort enrollment, the generation of each quantitative PET/MRI metric will be independently scored as a dichotomous variable; successful or non-successful. Proportional assessment will be performed to assess for project feasibility. The estimated proportion of success rate for each metric along with the corresponding 95% binomial confidence interval will be provided.
Time frame: Two days of diagnostic imaging
SELFI and hypoxic fraction, and T1 ferumoxytol Fe/gadolinium (Gd) log mismatch ratio in patients receiving immunotherapy
Diagnostic performance of PET/MRI metrics (SELFI and hypoxic fraction) and Gd\_MRI to differentiate progression from neuroinflammation (pseudoprogresion) will be evaluated using sensitivity, specificity and area under the receiver operating curve (AUROC). Sensitivity and specificity will be characterized using proportions and exact 95% confidence intervals. Difference in diagnostic performance between PET/MRI metrics (SELFI and hypoxic fraction) and Gd\_MRI will be assessed using McNemar's test to compare sensitivity and specificity and using the DeLong test to compare AUROC.
Time frame: Two days of diagnostic imaging at time of suspected progression
SELFI and hypoxic fraction, and T1 ferumoxytol Fe/gadolinium (Gd) log mismatch ratio in all patients
Diagnostic performance of PET/MRI metrics (SELFI and hypoxic fraction) and Gd\_MRI to differentiate progression from neuroinflammation (pseudoprogresion) will be evaluated using sensitivity, specificity and AUROC. Sensitivity and specificity will be characterized using proportions and exact 95% confidence intervals. Difference in diagnostic performance between PET/MRI metrics (SELFI and hypoxic fraction) and Gd\_MRI will be assessed using McNemar's test to compare sensitivity and specificity and using the DeLong test to compare AUROC.
Time frame: Two days of diagnostic imaging at time of suspected progression
Successful co-registration (Yes vs. No)
The generation of co-registered imaging data sets will be independently scored as a dichotomous variable; successful or non-successful (\< 10mm versus \[vs.\] \> 10mm alignment error). Proportional assessment will be performed to assess for project feasibility. The estimated proportion along with the corresponding 95% binomial confidence interval will be provided.
Time frame: Baseline to the start of long-term follow-up (up to 5 years)
T/B value and hypoxic tumor volume
Tumor-to-background ratio (TBR) is calculated by dividing the tumor SUV by the mean SUV of the background region, using either voxelwise values or summary measures such as SUVmean. To define hypoxic volume, a threshold-based approach is applied in which all tumor voxels with FMISO uptake above a predetermined TBR cutoff are classified as hypoxic; the hypoxic volume is then calculated as the total volume of these above-threshold voxels. Hypoxic volume is measured in mm3.
Time frame: Time Frame: Baseline to the start of long-term follow-up (up to 5 years)
Generation of SELFI Metric
Will assess generation of whole brain SELFI MRI data set. Generation of SELFI MRI: YES/NO.
Time frame: Imaging time points before gadolinium-based contrast agent defined presumed progression, year 1-4
SELFI diagnostic performance of imaging metrics
SELFI metric will be assessed to identify failed therapy at each imaging timepoint. Assessing Failed Therapy: Area Under the Curve for each metric at each time point to diagnose disease progression
Time frame: Imaging time points before gadolinium-based contrast agent defined presumed progression, year 1-4
Generation of Hypoxic Fraction Metric
Will assess generation of hypoxic fraction data set. Generation of hypoxic fraction: MRI YES/NO.
Time frame: Imaging time points before gadolinium-based contrast agent defined presumed progression, year 1-4
Hypoxic Fraction Diagnostic performance of imaging metric
Hypoxic Fraction metric will be assessed to identify failed therapy at each imaging timepoint. Assessing Failed Therapy: Area Under the Curve for each metric at each time point to diagnose disease progression.
Time frame: Imaging time points before gadolinium-based contrast agent defined presumed progression, year 1-4
Hypoxic fraction
Will determine the reproducibility of the pre-therapy FMISO PET imaging metrics as assessed by baseline "test" and "retest experiments. Reproducibility of hypoxic fraction between baseline "test" and "retest experiments will be evaluated by intra-class correlation coefficients (ICC).
Time frame: Retest will be scheduled within 7 days after the initial PET imaging examination, Baseline, year 1-4]
SELFI, hypoxic fraction and Modified Response Assessment in Neuro-Oncology (mRANO) criteria
Sensitivity, specificity and AUROC will be used to determine the diagnostic performance of imaging biomarkers (SELFI and hypoxic fraction, change in SELFI and hypoxic fraction between fraction between post-radiation therapy and suspected disease progression) and mRANO to differentiate progression from neuroinflammation (pseudoprogresion). Optimal cutoff points for SELFI and hypoxic fraction will be identified. Sensitivity and specificity will be characterized using proportions and exact 95% confidence intervals. McNemar's test will be used to compare sensitivity and specificity between imaging biomarkers and mRANO. Comparison of diagnostic performance with Gd MRI may also be explored.
Time frame: Year 1-5 at suspected disease progression
SELFI and hypoxic fraction
Will determine the sensitivity and specificity of SELFI hypoxic fraction for the diagnosis of neuroinflammation and recurrent disease. Sensitivity and specificity will be characterized using proportions and exact 95% confidence intervals. McNemar's test will be used to compare sensitivity and specificity between imaging biomarkers and mRANO. Comparison of diagnostic performance with Gd MRI may also be explored.
Time frame: Year 1-5 at suspected disease progression
Progression free survival (PFS)
Will be analyzed using the Kaplan-Meier product limit methods for all patients, taking censoring into account. A Cox regression model will be used to explore the association between imaging biomarkers and PFS while adjusting for patient characteristics.
Time frame: Date of diagnosis to date of progression, death or end of study, assessed up to 5 years
Overall survival (OS)
Will be analyzed using the Kaplan-Meier product limit methods for all patients, taking censoring into account. A Cox regression model will be used to explore the association between imaging biomarkers and OS while adjusting for patient characteristics.
Time frame: Date of diagnosis to date of progression, death or end of study, assessed up to 5 years
Change in SELFI and hypoxic fraction
Difference of SELFI or hypoxic fraction between post-radiation therapy and suspected disease progression
Time frame: From post-therapy to disease progression/pseudoprogression, year 1-5
SELFI
Will determine optimal SELFI imaging parameters. Outcome Measure: Optimal SELFI imaging echo time (TE) and repetition time (TR). Description: The optimal SELFI imaging parameters will be defined as the echo time (TE) and repetition time (TR) combination that demonstrates the highest correlation coefficient between SELFI and macrophage cellular density measured in tumor tissue samples. Unit of Measure: Milliseconds (ms).
Time frame: Baseline at year 1-3
SELFI and hypoxic fraction
Will assess correlation of SELFI hypoxic fraction with innate immune phenotype and hypoxia expression. Since innate immune phenotype is a binary variable (M1, or M2), differences in imaging metrics between M1 and M2 will be evaluated using two sample t-test. If normal assumption is not satisfied, data transformation, or 95% confidence intervals based on bootstrapping method will be used. Hypoxia expression will be measured by an ordinal variable (0,1,2,3,4) based on CA-9 expression, and correlation between SELFI/hypoxic fraction and hypoxia expression will be evaluated by Spearman's rank correlation coefficient.
Time frame: Year 1-4
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OHSU Knight Cancer Institute