Actively Recruiting
Oxidative Phosphorylation Targeting In Malignant Glioma Using Metformin Plus Radiotherapy Temozolomide
Led by Hopital Foch · Updated on 2025-11-21
640
Participants Needed
7
Research Sites
207 weeks
Total Duration
On this page
Sponsors
H
Hopital Foch
Lead Sponsor
N
National Cancer Institute, France
Collaborating Sponsor
AI-Summary
What this Trial Is About
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
Official Title
Oxidative Phosphorylation Targeting In Malignant Glioma Using Metformin Plus Radiotherapy Temozolomide
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Signed informed consent obtained before any study procedures
- Willingness and ability to comply with study treatment, visits, and follow-up
- Newly diagnosed, histologically confirmed supratentorial IDH wild-type glioblastoma (Grade 4 malignant glioma)
- Tumor shows OXPHOS+ subtype by central laboratory testing
- No prior treatment for glioblastoma except surgery
- Recovery from surgery without major ongoing safety issues
- On stable or no corticosteroid treatment (dexamethasone ≤ 6 mg or equivalent)
- Eastern Cooperative Oncology Group performance status 0-2
- Able to receive combined radiotherapy and chemotherapy per Stupp protocol
- Adequate bone marrow and liver function
- Creatinine clearance ≥ 30 mL/min (dose adjustment for 30-50 mL/min)
- Able to start radiotherapy within 7 weeks after diagnosis
- Life expectancy of at least 16 weeks
- Affiliated with appropriate health insurance
- Age 18 years or older
- Women of childbearing potential with negative pregnancy test within 7 days before study drug
- Women of childbearing potential agree to contraception during treatment and for 30 days after last dose
- Sexually active males agree to contraception during treatment and for 6 months after last dose
- White blood cells ≥ 2000/μL
- Neutrophils ≥ 1500/μL
- Platelets ≥ 100,000/μL
- Hemoglobin ≥ 9.0 g/dL
- Serum creatinine ≤ 1.5 times upper limit of normal or creatinine clearance ≥ 30 mL/min
- AST ≤ 3.0 times upper limit of normal
- ALT ≤ 3.0 times upper limit of normal
- Total bilirubin ≤ 1.5 times upper limit of normal (or ≤ 3.0 for Gilbert Syndrome patients)
You will not qualify if you...
- Prior glioblastoma treatment other than surgery, including Gliadel wafer
- Second primary cancer except treated non-melanoma skin cancer, treated in-situ cervical cancer, or other treated solid tumors with no disease for ≥ 5 years
- Known metastatic extracranial or leptomeningeal disease
- IDH mutant glioblastoma
- Secondary glioblastoma from prior lower-grade glioma
- Serious or uncontrolled medical disorder increasing study risk or interfering with treatment
- Unable to swallow oral medication or gastrointestinal disorders affecting absorption
- Pregnant or breastfeeding women
- Immunocompromised patients, including HIV positive on antiviral therapy
- Active hepatitis B or C infection
- Known allergy to metformin, temozolomide, or their components
- Severe renal insufficiency (creatinine clearance < 30 mL/min)
- Other central nervous system disorders unrelated to cancer unless controlled or non-interfering
- Unable or unwilling to have contrast-enhanced brain MRI
- Acute medical conditions impairing kidney function such as dehydration or severe infection
- Diseases causing tissue hypoxia like heart failure, respiratory failure, or recent heart attack
- Past diabetic precoma or acute metabolic acidosis
- Alcohol intoxication or alcoholism
- Persons under legal protection regimes
- Prisoners or involuntarily incarcerated individuals
- Patients compulsorily detained for psychiatric or infectious disease treatment
AI-Screening
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Trial Site Locations
Total: 7 locations
1
Foch Hospital
Suresnes, Hauts de Seine, France, 92150
Actively Recruiting
2
Hôpital Neurologique Pierre Wertheimer
Bron, Lyon, France, 69500
Actively Recruiting
3
Timone Hospital
Marseille, Marseille, France, 13354
Actively Recruiting
4
Saint Louis Hospital
Paris, Paris, France, 75010
Actively Recruiting
5
Pitié Salpêtrière Hospital
Paris, PARIS, France, 75013
Actively Recruiting
6
Istituto Nazionale Carlo Besta
Milan, Milano, Italy, 20131
Not Yet Recruiting
7
Spidali Riuniti Di Livorno
Livorno, Toscana Nord Ouest, Italy, 57100
Not Yet Recruiting
Research Team
A
Anna Luisa DI STEFANO, MD
CONTACT
E
Elisabeth HULIER-AMMAR, PhD
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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