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BMC Cancer
Published in: BMC Cancer 1/2024

Open Access 01-12-2024 | Glioblastoma | Study Protocol

A phase Ib/II randomized, open-label drug repurposing trial of glutamate signaling inhibitors in combination with chemoradiotherapy in patients with newly diagnosed glioblastoma: the GLUGLIO trial protocol

Authors: Maximilian Mastall, Patrick Roth, Andrea Bink, Angela Fischer Maranta, Heinz Läubli, Andreas Felix Hottinger, Thomas Hundsberger, Denis Migliorini, Adrian Ochsenbein, Katharina Seystahl, Lukas Imbach, Tibor Hortobagyi, Leonhard Held, Michael Weller, Hans-Georg Wirsching

Published in: BMC Cancer | Issue 1/2024

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Abstract

Background

Glioblastoma is the most common and most aggressive malignant primary brain tumor in adults. Glioblastoma cells synthesize and secrete large quantities of the excitatory neurotransmitter glutamate, driving epilepsy, neuronal death, tumor growth and invasion. Moreover, neuronal networks interconnect with glioblastoma cell networks through glutamatergic neuroglial synapses, activation of which induces oncogenic calcium oscillations that are propagated via gap junctions between tumor cells. The primary objective of this study is to explore the efficacy of brain-penetrating anti-glutamatergic drugs to standard chemoradiotherapy in patients with glioblastoma.

Methods/design

GLUGLIO is a 1:1 randomized phase Ib/II, parallel-group, open-label, multicenter trial of gabapentin, sulfasalazine, memantine and chemoradiotherapy (Arm A) versus chemoradiotherapy alone (Arm B) in patients with newly diagnosed glioblastoma. Planned accrual is 120 patients. The primary endpoint is progression-free survival at 6 months. Secondary endpoints include overall and seizure-free survival, quality of life of patients and caregivers, symptom burden and cognitive functioning. Glutamate levels will be assessed longitudinally by magnetic resonance spectroscopy. Other outcomes of interest include imaging response rate, neuronal hyperexcitability determined by longitudinal electroencephalography, Karnofsky performance status as a global measure of overall performance, anticonvulsant drug use and steroid use. Tumor tissue and blood will be collected for translational research. Subgroup survival analyses by baseline parameters include segregation by age, extent of resection, Karnofsky performance status, O6-methylguanine DNA methyltransferase (MGMT) promotor methylation status, steroid intake, presence or absence of seizures, tumor volume and glutamate levels determined by MR spectroscopy. The trial is currently recruiting in seven centers in Switzerland.

Trial registration

NCT05664464. Registered 23 December 2022.
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Metadata
Title
A phase Ib/II randomized, open-label drug repurposing trial of glutamate signaling inhibitors in combination with chemoradiotherapy in patients with newly diagnosed glioblastoma: the GLUGLIO trial protocol
Authors
Maximilian Mastall
Patrick Roth
Andrea Bink
Angela Fischer Maranta
Heinz Läubli
Andreas Felix Hottinger
Thomas Hundsberger
Denis Migliorini
Adrian Ochsenbein
Katharina Seystahl
Lukas Imbach
Tibor Hortobagyi
Leonhard Held
Michael Weller
Hans-Georg Wirsching
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2024
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-023-11797-z

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