Deuterium Metabolic Imaging to Assess Radiotherapy Changes in Glioblastoma Multiforme

Study Overview
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Brief Summary
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This is a feasibility single arm study designed for obtaining early data for optimization and evaluation of the clinical potential for a new MR technique using deuterated glucose. The purpose of the study is to investigate whether this technique is useful in metabolic imaging of glioblastoma multiforme (GBM) and whether radiochemotherapy (RCT) induced changes in the brain metabolism can be detected and might be predictive for treatment response. The study will include 10 patients with histologically verified GBM scheduled for standard RCT. Patients will have MRI scan performed before and within 8 weeks after starting RCT. The scans will include imaging after oral intake of deuterated glucose, so called deuterium metabolic imaging (DMI). Based on this study, the most optimal scanning technique, output variables of highest discriminative power with respect to RCT, and potential predictive markers for response will be selected for further clinical investigation.

Official Title
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Deuterium Metabolic Imaging to Assess Radiotherapy Changes in Glioblastoma Multiforme

Conditions
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Glioblastoma Multiforme

Intervention / Treatment
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* Diagnostic Test: Deuterium metabolic imaging


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with newly diagnosed GBM IDHwt Scheduled for long-course radiotherapy At least 18 years of age WHO performance status 0-1 Women who are not postmenopausal or surgically sterile must have a negative serum or urine pregnancy test performed at time of inclusion in the study. Safe and highly effective contraception must be used throughout the study meaning either hormonal anti-conception or an anti-fertility intrauterine device. Danish speaking Able and willing to comply after informed consent Exclusion Criteria: Subjects who are receiving any other investigational agents. Previous or current treatment by radiation or chemotherapy. History of alcohol abuse or illicit drug use. Contraindications to MRI Pacemaker, neurostimulator or cochlea implant Metal foreign bodies such as fragments and irremovable piercings Unsafe medical implants Intracranial clips or coils Claustrophobia Largest circumference including arms > 160 cm Contraindications to gadolinium contrast eGFR ≤ 30 mL/min/1.73m2 Previous adverse reactions to gadolinium Not able or willing to receive radiotherapy Predicted remaining survival <3 months Insulin-treated diabetes

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| GBM patients, IDH-wt<br> | Diagnostic Test: Deuterium metabolic imaging<br>* MRI after oral administration of 75g of [6,6'-2H2]glucose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Deuterium Metabolic Imaging | 2H-glucose uptake and conversion to lactate and glx over 120 minutes in normal brain and tumor tissue. Before and after radiochemotherapy to measure the changes with therapy. | Imaging repeated twice with  10 weeks between them. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Perfusion MRI | Dynamic contrast enhancement MRI using a gadolinium-based contrast agent. | Imaging repeated twice with  10 weeks between them. | 
| Microvascular diffusion MRI | Diffusion-weighted MRI. | Imaging repeated twice with  10 weeks between them. | 
| Amide proton transfer weighted MRI | APT-CEST MRI. | Imaging repeated twice with  10 weeks between them. | 
| Progression-free survival | Time until progression or death. | Until an event (average 6 months) or closure of the protocol after 4 years. | 
| Overall survival | Time until death. | Until an event (average 15 months) or closure of the protocol after 4 years. |