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.

Cancer neuroscience Epilepsy Gabapentin Memantine Sulfasalazine

Journal

BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800

Informations de publication

Date de publication:
15 Jan 2024
Historique:
received: 09 12 2023
accepted: 26 12 2023
medline: 16 1 2024
pubmed: 16 1 2024
entrez: 15 1 2024
Statut: epublish

Résumé

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. 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, O NCT05664464. Registered 23 December 2022.

Sections du résumé

BACKGROUND 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 METHODS
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, O
TRIAL REGISTRATION BACKGROUND
NCT05664464. Registered 23 December 2022.

Identifiants

DOI: 10.1186/s12885-023-11797-z PMID: 38225589
pubmed: 38225589
doi: 10.1186/s12885-023-11797-z
pii: 10.1186/s12885-023-11797-z
doi:

Banques de données

ClinicalTrials.gov
['NCT05664464']

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

82

Subventions

Organisme : Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
ID : 33IC30-198794

Informations de copyright

© 2024. The Author(s).

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Auteurs

Maximilian Mastall (M)

Department of Neurology, Clinical Neuroscience Center and Brain Tumor Center, University Hospital Zurich, Frauenklinikstrasse 26, Zurich, CH-8091, Switzerland.

Patrick Roth (P)

Department of Neurology, Clinical Neuroscience Center and Brain Tumor Center, University Hospital Zurich, Frauenklinikstrasse 26, Zurich, CH-8091, Switzerland.
Department of Neurology, University of Zurich, Zurich, Switzerland.

Andrea Bink (A)

Department of Neuroradiology, Clinical Neuroscience Center, University Hospital Zurich, Zurich, Switzerland.

Angela Fischer Maranta (A)

Department of Hematology and Oncology, Cantonal Hospital Graubünden, Chur, Switzerland.

Heinz Läubli (H)

Division of Medical Oncology, University Hospital Basel, Basel, Switzerland.

Andreas Felix Hottinger (AF)

Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

Thomas Hundsberger (T)

Department of Neurology and Medical Oncology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.

Denis Migliorini (D)

Department of Oncology, Hopitaux Universitaires de Genève, Geneva, Switzerland.

Adrian Ochsenbein (A)

Department of Medical Oncology, Inselspital, Bern University Hospital, Bern, Switzerland.

Katharina Seystahl (K)

Department of Neurology and Neurorehabilitation, Cantonal Hospital Lucerne, Lucerne, Switzerland.

Lukas Imbach (L)

Swiss Epilepsy Center - Klinik Lengg, Zurich, Switzerland.

Tibor Hortobagyi (T)

Department of Neuropathology, University Hospital Zurich, Zurich, Switzerland.

Leonhard Held (L)

Department of Biostatistics, Epidemiology Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland.

Michael Weller (M)

Department of Neurology, Clinical Neuroscience Center and Brain Tumor Center, University Hospital Zurich, Frauenklinikstrasse 26, Zurich, CH-8091, Switzerland.
Department of Neurology, University of Zurich, Zurich, Switzerland.

Hans-Georg Wirsching (HG)

Department of Neurology, Clinical Neuroscience Center and Brain Tumor Center, University Hospital Zurich, Frauenklinikstrasse 26, Zurich, CH-8091, Switzerland. hans-georg.wirsching@usz.ch.

Classifications MeSH