Oxidative Phosphorylation Targeting In Malignant glioma Using Metformin plus radiotherapy temozolomide

Phase 1

• Conditions: Patients with a diagnosis of Glioblastoma; MedDRA version: 20.0Level: PTClassification code 10018337Term: Glioblastoma multiformeSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10018336Term: GlioblastomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2021-000192-37-FR
• Lead Sponsor: Hôpital Foch

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-05-26
• Last Update Posted: 24 January 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 64

Inclusion Criteria

- Age = 18 years old
- Newly-diagnosed histologically-confirmed supra-tentorial glioblastoma (Grade IV malignant glioma by World Health Organization, including gliosarcoma), IDH wild-type glioblastoma
- OXPHOS+ subtype by the central laboratory
- No prior treatment for GBM other than surgery
- Substantial recovery from surgical resection, no major ongoing safety issues (eg, infection requiring IV antibiotics) following surgery
- Without corticosteroids or with stable dose of corticosteroids (ie = dexamethasone 6 mg, methylprednisolone 30 mg or prednisone 38 mg)
- ECOG performance status 0-2
- Able to receive concomitant radio-chemotherapy according to the Stupp protocol (60Gy) based on investigator judgment
- Adequate bone marrow and normal hepatic function
- Creatinine clearance =30 mL/min (between 30 and 50ml/min, patients will be prescribed no more than 1500mg of metformin)
- Able to start RT within 7 weeks after histological diagnosis
- Patients must have life expectancy = 16 weeks
-Patients affiliated to an appropriate health insurance system
- Provision of signed informed consent for selection and treatment phase obtained from the patient/legal representative prior to performing any protocol-related procedures
- 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
- WBC = 2000/µL
- Neutrophils = 1500/µL
- Platelets = 100 x103/µL
- Hemoglobin = 9.0 g/dL
- Serum creatinine = 1.5 x ULN or creatinine clearance (CrCl) = 30 mL/min (using the Cockcroft-Gault formula).
- AST = 3.0 x ULN
- ALT = 3.0 x ULN
- Total Bilirubin = 1.5 x ULN (except patients with Gilbert Syndrome who may have a total bilirubin < 3.0 x ULN)

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 32
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 32

Exclusion Criteria

- Prior treatment for GBM (other than surgical resection) including Gliadel Wafer
- 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
- Any known metastatic extracranial or leptomeningeal disease
- IDH mutant
- Secondary GBM (ie, progression from prior low-grade or anaplastic glioma)
- 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
- 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)
- Pregnant or breast-feeding women
- Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV) and are receiving anti-viral therapy
- Patients with known active hepatitis (i.e., HBV or HCV)
- Patients with a known hypersensitivity to metformin and temozolomide or any of the excipients of the products
- Patients with severe renal insufficiency ie, CrCl < 30 mL/min (who should not receive contrast materials)
- 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
- Patients unable (eg, due to pacemaker or ICD device) or unwilling to have a contrast-enhanced MRI of the head
- Any acute medical condition that may impair renal function such as dehydration, severe infection, shock
- Any disease which may cause tissue hypoxia such as decompensated heart failure, respiratory failure, recent myocardial infarction
- Diabetic precoma
- Acute metabolic acidosis
- Alcohol intoxication and Alcoholism
- Persons protected by a legal regime (guardianship, trusteeship).
- Prisoners or patients who are involuntarily incarcerated
-Patients who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified