Oxidative Phosphorylation Targeting In Malignant Glioma Using Metformin Plus Radiotherapy Temozolomide
Status:
Not yet recruiting
Trial end date:
2025-10-01
Target enrollment:
Participant gender:
Summary
Tailored approaches targeting crucial oncogenes and pathways have shown successful results in
a number of cancer types and offer exciting perspective in neuro-oncology. IDH (Isocitrate
dehydrogenase) wild-type (IDHwt) glioblastoma (GBM) (10%) present a unique and homogenous
energetic metabolism which is specifically dependent on the oxidative phosphorylation
(OXPHOS) rather than on the aerobic glycolysis. OXPHOS+ IDHwt GBMs overexpress mitochondrial
markers and can be specifically inhibited by mitochondrial inhibitors in vitro and in vivo.
Metformin is an oral inhibitor of mitochondrial complex I and is a widely used drug in
diabetic and non-diabetic patients, safe and well tolerated in association with radiotherapy
and chemotherapy.
Basing on drastic effect, the investigators have observed in vivo (reduction of >50% of tumor
growth) and hypothesize that metformin could be specifically efficient to treat up-front
patients affected by OXPHOS+ GBM, in association with the standard first-line treatment with
radiotherapy and temozolomide (RT-TMZ).
The investigators set up a dedicated molecular analysis including RNA assay and expression of
OXPHOS markers for formalin-fixed paraffin-embedded tumors (FFPE), which allows to detect
OXPHOS+ GBM at diagnosis.
Here a phase II, open label, non-randomized multicenter trial including five French
neurooncology centers (H. Foch-Suresnes, Pitié-Salpêtrière-Paris, Saint Louis-Paris, Lyon,
Marseille) and one in Italy (Istituto Besta, Milan) is proposed.
Newly diagnosed IDH wild-type GBM patients with the OXPHOS+ signature will be eligible for
inclusion in this trial. The investigators expect to screen 640 patients and to include 64
patients over a period of 24 months with 24 months of follow-up.