Oxygen-Enhanced MRI for Brain Tumors

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: OHSU Knight Cancer Institute

Disqualifiers: Pregnancy, Claustrophobia, Metallic implants, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method of using MRI scans to map oxygen levels in brain tumors. Tumors often have low oxygen, reducing the effectiveness of treatments like radiation and chemotherapy. Oxygen-enhanced MRI (Magnetic Resonance Imaging) aims to provide a clearer picture of tumor oxygen levels, allowing for more tailored treatments. The trial seeks adults with known or suspected brain tumors who are planning to undergo or have already received treatment. As an unphased trial, it offers patients a unique opportunity to contribute to innovative research that could enhance future treatment strategies.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that oxygen-enhanced MRI is safe for brain tumor patients?

Research has shown that oxygen-enhanced MRI, which involves breathing extra oxygen during the scan, is generally safe. Studies have found this method to be non-invasive and well-tolerated by patients. For instance, one study found it worked well for head and neck cancer patients without causing significant side effects. Another study noted that while researchers often use this technique in animal research, it is considered safe for humans too. Overall, evidence suggests no major safety concerns with oxygen-enhanced MRI, making it a promising option for understanding and treating brain tumors. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about oxygen-enhanced MRI for brain tumors because it offers a new way to visualize tumor oxygenation levels in real-time. Unlike standard MRI, which provides structural images, this technique involves patients breathing supplemental oxygen during the scan, potentially highlighting areas of the tumor that are more or less oxygenated. This could help tailor treatments more precisely, as tumor oxygenation is known to affect how well tumors respond to therapies like radiation. By enhancing the MRI with oxygen, doctors might better understand the tumor's environment, potentially leading to more effective treatment plans.

What evidence suggests that oxygen-enhanced MRI is effective for generating hypoxia maps in brain tumors?

Research has shown that oxygen-enhanced MRI (OE-MRI), which participants in this trial will undergo, can effectively detect low oxygen levels in brain tumors. During the trial, patients receive supplemental oxygen while undergoing standard MRI, resulting in clearer images of the tumor. This method measures low oxygen levels without surgery or other invasive procedures. Understanding oxygen levels in tumors is crucial because low levels can reduce the effectiveness of radiation and chemotherapy. By gaining insights into tumor oxygenation, doctors can adjust treatments to improve outcomes for each patient. ^{1 3 6 7 8}

Who Is on the Research Team?

Ramon Barajas

Principal Investigator

OHSU Knight Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults over 18 with a suspected or known brain tumor larger than 10 mL. Participants must be able to consent, have a performance score indicating they can carry out daily activities, and may already be receiving treatment for the tumor. It's not suitable for those with sickle cell disease, poor vein access, pregnancy, certain metal implants, severe other illnesses or conditions that make MRI or oxygen therapy risky.

Inclusion Criteria

Able to provide informed written consent and/or acceptable surrogate capable of providing consent on the patient's behalf

I am planning or have had treatment for a brain tumor.

I am an adult with a brain tumor.

Exclusion Criteria

Claustrophobia

I should avoid extra oxygen due to my severe lung or breathing condition.

I do not have any serious illnesses that could affect my participation in the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Diagnostic Imaging

Patients receive supplemental oxygen while undergoing standard of care MRI to generate hypoxia maps

1 hour

1 visit (in-person)

Follow-up

Participants are monitored for progression free survival and other outcomes

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Magnetic Resonance Imaging
• Oxygen Therapy

Trial Overview The study tests if oxygen-enhanced MRI can create detailed maps of low-oxygen areas in brain tumors. This non-invasive technique could help understand how much of the tumor lacks oxygen which affects treatment effectiveness like radiation and chemotherapy.

How Is the Trial Designed?

Group I: Diagnostic (oxygen-enhanced MRI) Experimental Treatment 2 Interventions

Patients receive supplemental oxygen while undergoing standard of care MRI.

Magnetic Resonance Imaging is already approved in United States for the following indications:

Approved in United States as Lumakras (sotorasib) for:

• Non-small cell lung cancer with KRAS G12C mutation

Approved in United States as Vectibix (panitumumab) for:

• Advanced colorectal cancer that is wild-type RAS

Who Is Running the Clinical Trial?

OHSU Knight Cancer Institute

Lead Sponsor

Trials

239

Recruited

2,089,000+

Oregon Health and Science University

Collaborator

Trials

1,024

Recruited

7,420,000+

Published Research Related to This Trial

Hyperoxic BOLD-MRI can effectively differentiate between breast cancer molecular subtypes, such as luminal A, Her2+, and triple-negative, using varying levels of oxygen, with significant differences observed even at 41% oxygen.

This imaging technique shows promise as a non-invasive biomarker for identifying luminal A breast cancer without the need for injected contrast agents, highlighting its potential for safer diagnostic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperoxic BOLD-MRI-Based Characterization of Breast Cancer Molecular Subtypes Is Independent of the Supplied Amount of Oxygen: A Preclinical Study. Bartsch, SJ., Ehret, V., Friske, J., et al.[2023]

Tumor oxygenation is crucial for the effectiveness of cancer treatments like radiation and chemotherapy, and hypoxic tumors are known to be resistant to these therapies, highlighting the need for accurate assessment methods.

Noninvasive imaging techniques, particularly blood oxygen level-dependent (BOLD) MR imaging, show promise in evaluating brain tumor oxygenation, which could enhance treatment planning and monitoring by identifying patients who may benefit from oxygenation strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypoxia imaging in brain tumors. Yetkin, FZ., Mendelsohn, D.[2019]

The study compared MRI signal changes with direct pO2 measurements in tumors of Balb-c mice with osteosarcoma, revealing that hyperoxia (breathing pure oxygen) affects tumor oxygen levels.

During oxygen inhalation, both increases and decreases in MR-signal intensity were observed, indicating a complex response of tumors to changes in oxygen supply, particularly as the hypoxic tumor fraction decreased.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison study of oxygen-induced MRI-signal changes and pO2 changes in murine tumors. Weissfloch, L., Peller, M., Weber, J., et al.[2019]

Functional MR imaging can effectively visualize changes in tumor oxygenation and blood flow in a rat brain tumor model, indicating its potential as a non-invasive assessment tool for tumor characteristics.

The study demonstrated that fMR imaging can differentiate between viable tumor regions and necrotic areas, providing insights into tumor growth and response to treatments like acetazolamide, which may enhance the evaluation of anti-cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional magnetic resonance (fMR) imaging of a rat brain tumor model: implications for evaluation of tumor microvasculature and therapeutic response. Mazurchuk, R., Zhou, R., Straubinger, RM., et al.[2019]

The study demonstrated that hemodynamic response imaging (HRI) using BOLD imaging during hyperoxic challenge is a safe and effective non-invasive method for assessing brain hemodynamic function in glioblastoma, providing valuable clinical information.

In an orthotopic mouse model, the anti-VEGF antibody B20-4.1.1 delayed tumor progression without significantly altering HRI results, while histological analysis showed reduced tumor vascularity and increased cell proliferation in treated tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monitoring brain tumor vascular heamodynamic following anti-angiogenic therapy with advanced magnetic resonance imaging in mice. Laufer, S., Mazuz, A., Nachmansson, N., et al.[2020]

In a study involving eight patients with brain tumors, the response of contrast-enhancing lesions to oxygen was significant, showing a 20.7% increase in T2* values, regardless of the gas administration protocol used.

However, the response to carbogen (a mixture of carbon dioxide and oxygen) was significantly influenced by the order of gas administration, with one protocol showing an increase of 18.6% and the other a decrease of 6.4%, highlighting the importance of gas administration order in interpreting MRI results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dependency of the blood oxygen level dependent-response to hyperoxic challenges on the order of gas administration in intracranial malignancies. Stieb, S., Riesterer, O., Boss, A., et al.[2020]

A study involving 10 participants with untreated glioma and 3 healthy volunteers used dynamic 17O MRI to measure cerebral metabolic rate of oxygen (CMRO2), revealing that glioma tumors exhibit significantly reduced CMRO2 compared to normal brain tissue, consistent with the Warburg effect.

The findings confirm that glioma tumors rely less on oxidative metabolism and more on glycolysis for energy, highlighting the potential of 17O MRI as a tool for understanding metabolic changes in brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative Dynamic Oxygen 17 MRI at 7.0 T for the Cerebral Oxygen Metabolism in Glioma. Paech, D., Nagel, AM., Schultheiss, MN., et al.[2020]

A new human-sized pulse EPROI instrument was successfully developed and tested for oxygen imaging in a rabbit model, marking a significant advancement in tumor hypoxia research.

The study demonstrated that systemic intravenous injection of the oxygen-sensitive spin probe OX071 can effectively cover tumors, paving the way for potential clinical applications in cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxygen Imaging of a Rabbit Tumor Using a Human-Sized Pulse Electron Paramagnetic Resonance Imager. Epel, B., Viswakarma, N., Sundramoorthy, SV., et al.[2023]

Oxygen-Enhanced MRI (dOE-MRI) effectively detects changes in tumor oxygenation following VEGF-ablation therapy, indicating its potential as a non-invasive biomarker for monitoring treatment response in radiation oncology.

The study demonstrated that dOE-MRI can reveal increased tissue oxygenation and reduced hypoxia in tumors, which correlates with enhanced sensitivity to radiation, suggesting that this imaging technique could improve cancer treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiosensitizing oxygenation changes in murine tumors treated with VEGF-ablation therapy are measurable using oxygen enhanced-MRI (OE-MRI). Baker, JHE., Moosvi, F., Kyle, AH., et al.[2023]

Multi-site electron paramagnetic resonance (EPR) oximetry allows for repeated and simultaneous measurements of oxygen levels (pO2) in gliomas and surrounding brain tissue, providing valuable insights into tumor hypoxia over time.

The study found that different glioma types exhibited varying levels of oxygenation, with some tumors being hypoxic, which could inform strategies to optimize oxygen-dependent therapies like chemoradiation by timing treatments when tumor oxygen levels are higher.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repeated assessment of orthotopic glioma pO(2) by multi-site EPR oximetry: a technique with the potential to guide therapeutic optimization by repeated measurements of oxygen. Khan, N., Mupparaju, S., Hou, H., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10230402/

T1 based oxygen-enhanced MRI in tumours: research review In conclusion, there is strong pre-clinical evidence of the utility of OE-MRI in assessing and monitoring tumour hypoxia, however, significant clinical work ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2405630825000308

MRI for Brain Tumor Hypoxia: Validation Study Review MRI is a widely available imaging modality that can potentially evaluate tumor hypoxia without ionizing radiation in a non- or minimally-invasive manner. Below, ...

3. withpower.com withpower.com/trial/phase-brain-neoplasms-3-2023-9a95f

Oxygen-Enhanced MRI for Brain Tumors · Info for Participants Oxygen-Enhanced MRI (OE-MRI) is unique because it uses inhaled oxygen as a contrast agent to non-invasively measure the oxygen levels in brain tumors, which can ...

4. oncotarget.com oncotarget.com/article/16256/text/

Investigation of hypoxia conditions using oxygen ... In conclusion, the findings of this study provide evidence that OE-MRI can produce reliable measurements to detect tumor hypoxia in a rat model.

5. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1306164/full

The MANGO study: a prospective investigation of oxygen ... In this clinical study, we aim to investigate the role of oxygen enhanced (OE) and blood-oxygen level dependent (BOLD) MRI as non-invasive imaging biomarkers ...

6. aacrjournals.org aacrjournals.org/cancerrescommun/article/4/10/2565/748751/Combined-Oxygen-Enhanced-MRI-and-Perfusion-Imaging

Combined Oxygen-Enhanced MRI and Perfusion Imaging ... Oxygen-enhanced MRI (OE-MRI) has shown promise for quantifying and spatially mapping tumor hypoxia, either alone or in combination with perfusion imaging.

7. cancerresearchuk.org cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-study-looking-at-a-new-type-of-mri-scan-for-people-with-lung-cancer-or-a-solid-tumour

A study looking at a new type of MRI scan for people with ... The study team found that the OE-MRI scan can be used to identify areas of the cancer that have low oxygen levels.

8. eurradiolexp.springeropen.com eurradiolexp.springeropen.com/articles/10.1186/s41747-024-00429-1

Oxygen-enhanced MRI assessment of tumour hypoxia in head ... Oxygen-enhanced MRI assessment of tumour hypoxia in head and neck cancer is feasible and well tolerated in the clinical setting.