Cerveau (SNC)

TITRE	Metformine avec témozolomide néo-adjuvant et radiothérapie accélérée hypofractionnée à marge minimale suivis de témozolomide adjuvant auprès de patients atteints de glioblastome multiforme
PROTOCOLE ID	MUHC ID: 4315 (M-HARTT STUDY)
CLINICAL TRIAL.gov ID	NCT02780024
TYPE(S) DE CANCER	Cerveau (SNC)
PHASE	Phase II
TYPE D'ÉTUDE
INSTITUTION	CENTRE UNIVERSITAIRE DE SANTE MCGILL 1001 boul. Décarie
VILLE	Montréal
INVESTIGATEUR(RICE) PRINCIPAL(E)	George Shenouda
COORDONATEUR(RICE)	Marianna Perna marianna.perna@muhc.mcgill.ca 514-934-1934 poste 43191
STATUT	Fermé
CRITÈRES D'ÉLIGIBILITÉ	(EN) Age: 18 years or older Histological confirmation of supra-tentorial GBM KPS > 60 Neurological function 0 or 1 Adequate bone marrow as defined below: Absolute neutrophil count (ANC) ≥ 1500 cells/mm3. Platelets ≥ 100,000 cells/mm3 Hemoglobin ≥ 10 g/dl. Adequate renal function, as defined below: Creatinine clearance of >60 ml/min/1.73m2 (using the Cockcroft Gault equation for eGFR) within 14 days prior to study registration Adequate hepatic function, as defined below: Bilirubin of 1.7 to 18.9 umol/L within 14 days prior to study registration ALT ≤ 3 x normal range within 14 days prior to study registration Neo-adjuvant TMZ and Metformin to start within 4 weeks of surgery Concomitant TMZ and Metformin and accelerated Hypofractionated EBRT to start at least 2 weeks after adjuvant TMZ starting date, and no later than five weeks from surgery. Surgical diagnosis/intervention may include: partial or near total resection Patients must have recovered from the effects of surgery, postoperative infection and other complications before study registration. A diagnostic contrast-enhanced MRI or CT scan of the brain must be performed preoperatively and postoperatively. The postoperative scan must be done within 28 days prior to the initiation of neo-adjuvant TMZ. Preoperative and postoperative scans must be the same type. Patients unable to undergo MR imaging can be enrolled provided pre- and post-operative contrast-enhanced CT scans are obtained and are of sufficient quality. History/physical examination, including neurologic exam within 14 days prior to study registration. Documentation of steroid doses within 14 days prior to study registration and stable or decreasing steroid dose within 5 days prior to registration. For females of child-bearing potential, negative serum pregnancy test within 72hours prior to starting TMZ and Metformin. Women of childbearing potential and male participants must practice adequate contraception. Adequate tissue specimen for MGMT status analysis. Able to sign an informed study-specific consent
CRITÈRES D'EXCLUSION	(EN) Diabetic patients both type I and type II. No tissue provided for MGMT promoter methylation status determination. Margin of contrast-enhanced residual mass closer than 15 mm from the optic chiasm or optic nerves. Prior invasive malignancy (except for non-melanoma skin cancer) unless disease free for ≥ 3 years Recurrent or multifocal GBM. Prior chemotherapy or radio-sensitizers for cancers of the head and neck region; prior chemotherapy for a different cancer is allowable. Severe, active co-morbidity, defined as follows: Acute or chronic renal failure. Unstable angina and/or congestive heart failure requiring hospitalization Transmural myocardial infarction within the last 6 months Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration. Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition. Major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy. Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic. Pregnant or lactating women, due to possible adverse effects on the developing foetus or infant due to study drug. Prior allergic reaction to Temozolomide or Metformin. Patients treated on any other therapeutic clinical protocols within 30 days prior to study entry or during participation in the study