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NCT Number: NCT05500612

MRI Hypoxia Study for Glioblastoma Multiforme (GBM) Radiation Therapy

This study is designed to evaluate the role of Oxygen Enhanced (OE) Magnetic resonance imaging (MRI) and Blood Oxygenation Level Dependent (BOLD) MRI in detecting regions of hypoxic tumour and to evaluate their use as imaging methods to selectively deliver targeted radiotherapy to regions of aggressive disease.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

North Shore Private Hospital, St Leonards, New South Wales, Australia

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About this study

The ability to image tumour hypoxia at diagnosis and prior to radiotherapy is extremely important to appropriately adapt radiotherapy plans such that to selectively deliver higher doses of radiation to those more aggressive tumour subregions, thereby improving the chances to achieve better local tumour control. Preoperative imaging of tumour hypoxia also offers the opportunity for 'supra-marginal resections' in surgical planning beyond current neurosurgical standard of care. Additionally, accurately identifying regions of tumour hypoxia harbouring tumour progression at follow up is fundamental in patient follow-up, allowing multidisciplinary teams to more confidently intervene at an earlier stage of tumour recurrence and personalise therapy tailored to the tumour's response to treatment. Routine imaging of tumour hypoxia is currently challenging, as it requires [18F]-Fluoromisonidazole (18F-FMISO PET) imaging, which is not available in the majority of clinical centres. Today, the availability of accelerated quantitative MRI sequences on clinical MRI systems could enable quantification of tumour hypoxia without putting an unfeasible burden on patients' scan sessions. The next frontier in radiotherapy treatment will use these techniques to identify hypoxic tumour tissues and personalise treatments to the patient's unique tumour biology, maximising the probability of tumour control.

This clinical study will acquire additional images of brain cancer patients. The images will not change the patient's treatment. This study is designed to evaluate the role of oxygen enhanced (OE) MRI and BOLD MRI in detecting regions of hypoxic tumour and to evaluate their use as imaging methods to selectively deliver targeted radiotherapy to regions of aggressive disease.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Suspected high-grade glioma (HGG) / glioblastoma multiforme (WHO grade IV) at initial radiological examination
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2
  • Available for scanning on two separate days

Exclusion criteria

  • Women lactating, pregnant or of childbearing potential who are not willing to avoid pregnancy during the study
  • Patients with a history of severe renal disease(s) (eGFR <20) that cannot tolerate gadolinium chelate contrast agents.
  • Geographically remote patients unable to agree to imaging schedule
  • Patients who have received anti - vascular endothelial growth factor (anti-VEGF) monoclonal antibody therapy the 3 months prior to recruitment
  • Patients with a history of psychological illness or condition such as to interfere with the patient's ability to understand the requirements of the study.
  • Patients with significant cardiac or pulmonary disease including cardiac arrythmias or Chronic Obstructive Pulmonary Disease (COPD) that are unable to tolerate high flow O2 for oxygen contrast.
  • Patients taking carbonic anhydrase inhibitors (Acetazolamide)
  • History of glaucoma
  • Any implant, foreign body, 3 Tesla (3T) MRI incompatible device, or other contraindication to MRI imaging.

Treatment and study plan

Primary outcomes

  1. Determination of spatial correlation of hypoxic tumour volume between Magnetic resonance imaging (MRI) and [18F]-Fluoromisonidazole (18F-FMISO) MRI

    Time frame: 1 year

    Spatial correlation between hypoxic tumour volume determined with MRI and 18F-FMISO will be evaluated via measurements of Dice similarity coefficient. Dice similarity coefficients > 0.9 will be considered a strong spatial correlation. Quantitative correlation of voxel-wise levels of hypoxia will be evaluated via measurement of the Spearman's/Pearson's correlation coefficient. Correlation coefficients > 0.7 will be considered a strong correlation.

Secondary outcomes

  1. Repeatability of voxel-wise levels of hypoxia in the tumour

    Time frame: 1 year

    Repeatability of voxel-wise levels of hypoxia in the tumour will be assessed by measurements of intraclass correlation coefficient (ICC).27 ICC values > 0.9 reflect excellent repeatability, good between 0.75 and 0.9, moderate between 0.5 and 0.75, and poor < 0.5. Additionally, similarity between the hypoxia tumour volume (HTV) defined with the MRI biomarker at the two timepoints will be assessed via calculation of Dice similarity coefficient. Dice similarity coefficients > 0.9 will be considered a strong correlation.

  2. The predicted patient outcomes of the biologically-adapted Radiotherapy (RT) plan will be compared with the actual patient outcomes

    Time frame: 1 year

    The predicted patient outcomes of the biologically-adapted RT plan will be compared with the actual patient outcomes following conventional treatment, by using metrics including tumour control probability (TCP) and toxicity measurement to organs at risks and healthy brain (including equivalent uniform dose). Success for this objective will be achieved if the biologically-adapted RT plans result in improved TCP by at least 10% for all patients over conventional treatment, while toxicity metrics remain similar.

  3. Correlation between the percentage of hypoxic tumour volume and clinical outcome

    Time frame: 1 year

    Correlation between the percentage of hypoxic tumour volume and clinical outcome will be evaluated by means of hazard ratio obtained from Cox regression. A hazard ratio > 1 (p<0.05) will indicate that the hypoxic tumour volume increase from 13 weeks post chemoradiation therapy (CRT) and recurrence is associated with worst Overall Survival (OS) and Progression Free Survival (PFS).

  4. Correlation between the percentage change of hypoxic tumour volume during treatment and clinical outcome

    Time frame: 1 year

    Correlation between the percentage change of hypoxic tumour volume during treatment and clinical outcome will be evaluated by means of hazard ration obtained from Cox regression. A hazard ratio > 1 (p<0.05) will indicate that the increase in hypoxic tumour volume during treatment is associated with worse OS.

Study contacts

Contact information is provided by the study sponsor or research team.

David Waddington

CONTACT

[email protected]

Shona Silvester

CONTACT

[email protected]

+61286271185

Sponsors and collaborators

Lead sponsor

University of Sydney

Other

Collaborators

  • The Brain Cancer Group

Registry information

Official study title

Magnetic Resonance Imaging of Hypoxia for Radiation Treatment Guidance in Glioblastoma Multiforme (MANGO)

Acronym: MANGO

Important dates

Study start
2024
Primary completion
2026
Study completion
2026
First posted
Aug 15, 2022
Registry last updated
May 19, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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