System Maintenance Notice

Please note that maintenance work is scheduled between 4 AM and 5 AM - CET. During this time, you may experience reduced performance. Thanks for your patience.

Studies

Interventional Recruiting Phase 2

NCT04945148 on ClinicalTrials.gov

Oxidative Phosphorylation Targeting In Malignant Glioma Using Metformin Plus Radiotherapy Temozolomide

  • Sponsor: Hôpital Foch
  • Collaborators: National Cancer Institute, France
  • Enrollment: 640 (Estimated)
  • Study start: 2024-05-10 (Actual)
  • Primary completion: 2028-05-01 (Estimated)
  • Study completion: 2028-05-01 (Estimated)
  • Allocation: N/a
  • InterventionModel: Single Group
  • InterventionModelDescription: Metformin (1500 to 3000mg/day) in addition to Stupp protocol, starting 7 days before the start of the standard radiotherapy (RT, 60Gy/6 weeks), concomitant Temozolomide (TMZ) chemotherapy (75mg/m²/day), and adjuvant TMZ (150-200 mg/m 2/ 5 days) + metformin will follow onwards until the 12th cycle of TMZ
  • Masking: None
  • PrimaryPurpose: Treatment

Brief 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.

Conditions

  • Glioblastoma, IDH-wildtype

Intervention / Treatment

  • Drug: Metformin
  • Radiation: Radiation IMRT
  • Drug: Temozolomide

Primary Outcome Measures

  • Assessement of Progression Free Survival (PFS) of patients with newly-diagnosed IDH wild-type OXPHOS + GBM (either with or without FGFR3-TACC3 gene fusion) treated with RT plus TMZ combined with metformin (During the 24 months of follow-up)
    Progression free survival (PFS) estimated by the RANO (Response Assesment in Neuro Oncology) criteria

Countries

France, Italy

Locations and Investigators

  • Hopital Saint Louis, Paris, France
    • Stefania, Cuzzubbo
  • Timone University Hospital, Marseille, France
    • Emeline, TABOURET
  • Hospital Foch, Suresnes, France
    • YOUNAN, Nadia
  • Hopitaux Universitaires Pitie Salpetriere, Paris, France
    • Marc, SANSON
  • Hospices Civils De Lyon, Bron, France
    • François, DUCRAY

Study Officials

  • Anna Luisa DI STEFANO, MD (Principal Investigator) — Foch Hospital