Feasibility of FMISO in Brain Tumors

NCT03649880 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: STUDY00016043R37CA288577NCI-2018-01479
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

IDH Wild Type Glioblastoma

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  Two days of diagnostic imaging at time of suspected progression

Secondary Outcomes (14)

• Successful co-registration (Yes vs. No)

  Baseline to the start of long-term follow-up (up to 5 years)

• T/B value and hypoxic tumor volume

  Time Frame: Baseline to the start of long-term follow-up (up to 5 years)

• Generation of SELFI Metric

  Imaging time points before gadolinium-based contrast agent defined presumed progression, year 1-4

• SELFI diagnostic performance of imaging metrics

  Imaging time points before gadolinium-based contrast agent defined presumed progression, year 1-4

• Generation of Hypoxic Fraction Metric

  Imaging time points before gadolinium-based contrast agent defined presumed progression, year 1-4

Study Arms (1)

Diagnostic (FMISO, PET/MRI or PET/CT)

EXPERIMENTAL

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

Interventions

¹⁸F-Fluoromisonidazole DRUG

Given IV

Also known as: ¹⁸F-MISO, ¹⁸F-Misonidazole, FMISO

Diagnostic (FMISO, PET/MRI or PET/CT)

Computed Tomography PROCEDURE

Undergo PET/CT

Also known as: CAT, CAT Scan, Computerized Axial Tomography, Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography

Diagnostic (FMISO, PET/MRI or PET/CT)

Magnetic Resonance Imaging PROCEDURE

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

Diagnostic (FMISO, PET/MRI or PET/CT)

Positron Emission Tomography PROCEDURE

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

Diagnostic (FMISO, PET/MRI or PET/CT)

Oxygen Therapy PROCEDURE

Receive supplemental oxygen

Also known as: supplemental oxygen therapy

Diagnostic (FMISO, PET/MRI or PET/CT)

Ferumoxytol DRUG

Given IV

Also known as: Feraheme, Ferumoxytol, ferumoxytol, FERUMOXYTOL NON-STOICHIOMETRIC MAGNETITE, Ferumoxytol Non-Stoichiometric Magnetite

Diagnostic (FMISO, PET/MRI or PET/CT)

Gadolinium DRUG

Given IV

Diagnostic (FMISO, PET/MRI or PET/CT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients (18 years of age and older) with a clinically suspected glioma
• Able to provide informed written consent and/or acceptable surrogate capable of providing consent on the patient's behalf
• Legally authorized representative (LAR)-signed informed consent and assent obtained for those subjects identified as decisionally impaired
• Intracranial disease greater than 5 mL as assessed by T2/fluid attenuated inversion recovery (FLAIR) MR imaging
• Karnofsky performance score \> 60 or Eastern Cooperative Oncology Group (ECOG) \< 3 as assessed by referring clinician.
• Either has previously received therapeutic intervention for an intracranial tumor or is eligible for and agreeable to receiving standard of care stupp protocol radiation and temozolomide after biopsy or maximum safe surgical resection
• Life expectancy of at least 6 months
• Female subject of childbearing potential will be asked for possibility of pregnancy. If unsure of pregnancy status, then a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study drug (FMISO). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• Adequate organ function as demonstrated by a chart review of platelets, renal, hepatic, and coagulation. We will follow the Department of Diagnostic Radiology clinical policy for assessing renal function prior to injecting gadolinium-based contrast. If there is a history of poor kidney function, a point of care serum creatinine test may be performed to ensure adequate kidney function prior to FMISO administration. If there is a history of any other poor organ function, we will not administer Ferumoxytol, but the subject may receive all other study interventions

You may not qualify if:

• Pregnant or breastfeeding.
• Contraindication to PET, MRI, FMISO, ferumoxytol, or intravenous gadolinium based contrast agents.
• Claustrophobia is not controlled with medical therapy
• Weight is greater than modality maximum capacity.
• Presence of metallic foreign body or implanted medical devices in body not documented as MRI safe according to the Oregon Health \& Science University (OHSU) Department of Radiology guidelines (including but not limited to cardiac pacemaker, aneurysm clips, surgical clips, prostheses, artificial hearts, valves with steel parts, metal fragments, shrapnel, tattoos near the eye, or steel implants).
• Subjects with family history of or known iron overload (genetic hemochromatosis).
• Subject who have received ferumoxytol within 3 weeks of study entry and require another ferumoxytol administration.
• Subjects with three or more drug allergies from separate drug classes.
• History of hypersensitivity allergic reactions attributed to compounds of similar chemical or biologic composition to FMISO. An allergic reaction to nitroimidazoles is highly unlikely.
• Sickle cell disease.
• History of hypersensitivity allergic reactions attributed to compounds of similar chemical or biologic composition to ferumoxytol or gadolinium MRI contrast
• Unsure of pregnancy status as assessed by Department of Radiology and AIRC guidelines.
• Subjects for whom supplemental oxygen could be harmful such as people with potential for hypoventilation (end-stage chronic obstructive pulmonary disease \[COPD\], obstructive sleep apnea \[OSA\] on continuous positive airway pressure \[CPAP\]/biphasic positive airway pressure \[Bi-PAP\], etc).
• Presence of any other co-existing condition that, in the judgment of the principal investigator, might increase the risk to the subject (i.e., plans for hospice or end of life care).
• Poor peripheral intravenous access evaluated by patient history.

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead
• National Cancer Institute (NCI): collaborator
• Oregon Health and Science University: collaborator

Study Sites (1)

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

RECRUITING

MeSH Terms

Interventions

fluoromisonidazole; Magnetic Resonance Spectroscopy; Oxygen; Ferrosoferric Oxide; Gadolinium

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques; Chalcogens; Elements; Inorganic Chemicals; Gases; Ferric Compounds; Iron Compounds; Ferrous Compounds; Minerals; Lanthanoid Series Elements; Metals, Rare Earth; Metals

Study Officials

• Ramon Barajas

  OHSU Knight Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 6, 2018
• First Posted: August 28, 2018
• Study Start: June 1, 2019
• Primary Completion (Estimated): January 31, 2029
• Study Completion (Estimated): January 31, 2030
• Last Updated: September 18, 2026

Record last verified: 2026-09

Locations

US (1)