MRI Hypoxia Study for Glioblastoma Multiforme (GBM) Radiation Therapy

Glioblastoma Multiforme Clinical Trial

— MANGO  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05500612
• Other study ID #: ETH11794
• Status: Not yet recruiting
• Start date: June 2024
• Est. completion date: December 2025

Study information

• Verified date: June 2024
• Source: University of Sydney
• Contact: Shona Silvester
• Phone: +61286271185
• Email: shona.silvester[@]sydney.edu.au
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20
• Est. completion date: December 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Glioblastoma
• Glioblastoma Multiforme
• Hypoxia

Locations

Country	Name	City	State
Australia	North Shore Private Hospital	St Leonards	New South Wales
Australia	Royal North Shore Hospital	St Leonards	New South Wales

Sponsors (2)

Lead Sponsor	Collaborator
University of Sydney	The Brain Cancer Group

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determination of spatial correlation of hypoxic tumour volume between Magnetic resonance imaging (MRI) and [18F]-Fluoromisonidazole (18F-FMISO) MRI	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.	1 year
Secondary	Repeatability of voxel-wise levels of hypoxia in the tumour	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.	1 year
Secondary	The predicted patient outcomes of the biologically-adapted Radiotherapy (RT) plan will be compared with the actual patient outcomes	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.	1 year
Secondary	Correlation between the percentage of hypoxic tumour volume and clinical outcome	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).	1 year
Secondary	Correlation between the percentage change of hypoxic tumour volume during treatment and clinical outcome	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.	1 year