Metformin hydrochloride for Glioblastoma (Grade 4)

Inclusion criteria

• {"criterion_text":"- Provision of signed informed consent for selection and treatment phase obtained from the patient/legal representative (for patients unable to give their consent by themselves according to the article L1121-8 of “Code de la Santé Publique”) prior to performing any protocol-related procedures"}
• {"criterion_text":"- Adequate bone marrow and normal hepatic function"}
• {"criterion_text":"- Creatinine clearance ≥30 mL/min (between 30 and 50ml/min, patients will be prescribed no more than 1500mg of metformin)"}
• {"criterion_text":"- Able to start RT within 7 weeks after histological diagnosis"}
• {"criterion_text":"- Patients must have life expectancy ≥ 16 weeks"}
• {"criterion_text":"- Patients affiliated to an appropriate health insurance system."}
• {"criterion_text":"- Age ≥ 18 years old"}
• {"criterion_text":"- Women of childbearing potential (WOCBP) must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 7 days prior to the start of study drug"}
• {"criterion_text":"- Women of childbearing potential (WOCBP) must agree to follow instructions for method(s) of contraception from the signing of the informed consent and continue throughout period of taking study treatment and for 6 months after last dose of study drug plus the time required for the investigational drug to undergo five half-lives (both TMZ and metformin). The terminal half-life of temozolomide is 1.8 hours. The terminal half-life for metformin is 6.5 hours."}
• {"criterion_text":"- Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception throughout the period of taking study treatment and for 6 months plus the time required for the both investigational drug (metformin) and TMZ to undergo five half-lives. The terminal half-life of temozolomide is 1.8 hours. The terminal half-life for metformin is 6.5 hours"}
• {"criterion_text":"- WBC ≥ 2000/μL t) Neutrophils ≥ 1500/μL"}
• {"criterion_text":"- Patients must be willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits, and examinations including follow-up"}
• {"criterion_text":"- Platelets ≥ 100 x103/μL"}
• {"criterion_text":"- Hemoglobin ≥ 9.0 g/dL"}
• {"criterion_text":"- Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 30 mL/min (using the Cockcroft-Gault formula)"}
• {"criterion_text":"- AST ≤ 3.0 x ULN and ALT ≤ 3.0 x ULN and Total Bilirubin ≤ 1.5 x ULN (except patients with Gilbert Syndrome who may have a total bilirubin < 3.0 x ULN)"}
• {"criterion_text":"- Newly-diagnosed histologically-confirmed supra-tentorial glioblastoma IDH wild-type (Grade IV 4 malignant glioma by World Health Organization, including gliosarcoma)"}
• {"criterion_text":"- OXPHOS+ subtype by the central laboratory"}
• {"criterion_text":"- No prior treatment for GBM other than surgery"}
• {"criterion_text":"- Substantial recovery from surgical resection, no major ongoing safety issues (eg, infection requiring IV antibiotics) following surgery"}
• {"criterion_text":"- Without corticosteroids or with stable dose of corticosteroids (ie ≤ dexamethasone 6 mg, methylprednisolone 32 mg or prednisone 40mg)"}
• {"criterion_text":"- ECOG performance status 0-2"}
• {"criterion_text":"- Able to receive concomitant radio-chemotherapy according to the Stupp protocol (60Gy) based on investigator judgment"}

Exclusion criteria

• {"criterion_text":"- Prior treatment for GBM (other than surgical resection) including Gliadel Wafer"}
• {"criterion_text":"- Alcohol intoxication and Alcoholism"}
• {"criterion_text":"- Persons protected by a legal regime (guardianship, trusteeship"}
• {"criterion_text":"- Patients with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for ≥ 5 years"}
• {"criterion_text":"- Prisoners or patients who are involuntarily incarcerated"}
• {"criterion_text":"- Patients who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness"}
• {"criterion_text":"- Any known metastatic extracranial or leptomeningeal disease"}
• {"criterion_text":"- IDH mutant, K27 and NTRK alterations"}
• {"criterion_text":"- Secondary GBM (ie, progression from prior low-grade or anaplastic glioma)"}
• {"criterion_text":"- Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the patient to receive protocol therapy, or interfere with the interpretation of study results g) Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication (inflammatory bowel disease, major bowel resection) h) Pregnant or breast-feeding women"}
• {"criterion_text":"- Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV) and are receiving anti-viral therapy"}
• {"criterion_text":"- Patients with hypersensitivity to dacarbazine and rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption"}
• {"criterion_text":"- Patients with known active hepatitis (i.e., HBV or HCV)"}
• {"criterion_text":"- Patients with a known hypersensitivity to metformin and temozolomide or any of the excipients of the products"}
• {"criterion_text":"- Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication (inflammatory bowel disease, major bowel resection)"}
• {"criterion_text":"- Pregnant or breast-feeding women"}
• {"criterion_text":"- Patients with severe renal insufficiency ie, CrCl < 30 mL/min (who should not receive contrast materials)"}
• {"criterion_text":"- History or evidence upon physical/neurological examination of other central nervous system condition (eg, seizures, abscess) unrelated to cancer, unless adequately controlled by medication or considered not potentially interfering with protocol treatment"}
• {"criterion_text":"- Patients unable (eg, due to pacemaker or ICD device) or unwilling to have a contrast-enhanced MRI of the head"}
• {"criterion_text":"- Any acute medical condition that may impair renal function such as dehydration, severe infection, shock"}
• {"criterion_text":"- Any disease which may cause tissue hypoxia such as decompensated heart failure, respiratory failure, recent myocardial infarction"}
• {"criterion_text":"- Past diabetic precoma"}
• {"criterion_text":"- Past acute metabolic acidosis"}

Primary endpoints

• {"endpoint_text":"- Progression Free Survival estimated by the RANO criteria","definition_or_measurement_approach":"Progression Free Survival measured/estimated according to the RANO criteria"}

Secondary endpoints

• {"endpoint_text":"- ✓ Overall survival.","definition_or_measurement_approach":"Overall survival (OS) measured as time from enrolment/treatment to death from any cause"}
• {"endpoint_text":"- ✓ Overall response rate (ORR) estimated by the RANO criteria.","definition_or_measurement_approach":"Overall response rate assessed/estimated using the RANO criteria"}
• {"endpoint_text":"- ✓ Safety: type, frequency, and severity (grade III and IV toxicity) of AEs and SAEs.","definition_or_measurement_approach":"Safety assessed by recording type, frequency, and severity of adverse events and serious adverse events, with grading for grade III and IV toxicities"}
• {"endpoint_text":"- ✓ Dose interruptions, reductions, and dose intensity.","definition_or_measurement_approach":"Recorded instances of dose interruptions, reductions, and calculation of dose intensity"}
• {"endpoint_text":"- ✓ Time of occurrence and evaluations of laboratory values.","definition_or_measurement_approach":"Timing and evaluation of laboratory parameters as recorded per protocol"}
• {"endpoint_text":"- ✓ Several safety aspects will be recorded such as haematological toxicity (and related risks of infection and bleeding), hypersensitivity requiring treatment interruption, digestive effects (nausea, vomiting, constipation)","definition_or_measurement_approach":"Recording and monitoring of specific safety aspects including haematological toxicity, hypersensitivity events, and digestive adverse effects"}

France

Earliest CTIS Part Ii Submission Date

26-09-2024

Latest Decision Or Authorization Date

11-03-2026

Processing Time Days

531

Number Of Sites

5

Number Of Participants

59

Primary sponsor

Full Name

Hospital Foch

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France