Deuterium Metabolic Imaging to Assess Radiotherapy Changes in Glioblastoma Multiforme

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Glioblastoma Multiforme
• Intervention / Treatment: Diagnostic test: Deuterium metabolic imaging

• Study Type: Observational
• Enrollment (Estimated): 10

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark, 8200
    • Aarhus University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients with newly diagnosed GBM, idh-wt (performance 0-1) are enrolled before initiating radiochemotherapy. They are not allowed to have contraindications to MRI with contrast or diabetes.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
GBM patients, IDH-wt	Diagnostic test: Deuterium metabolic imaging; MRI after oral administration of 75g of [6,6'-2H2]glucose.

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: University of Aarhus

Study record dates

Study Major Dates

• Study Start (Actual): August 25, 2023
• Primary Completion (Estimated): August 1, 2024
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: May 15, 2023
• First Submitted That Met QC Criteria: June 6, 2023
• First Posted (Actual): June 18, 2023

Study Record Updates

• Last Update Posted (Actual): December 7, 2023
• Last Update Submitted That Met QC Criteria: November 30, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma
• Other Study ID Numbers: DMI-GBM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Data will be shared in anonymized form if the local juridical office accepts that full anonymization can be achieved.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No