Titre Metformin and Neo-adjuvant Temozolomide and Hypofractionated Accelerated Limited-margin Radiotherapy Followed by Adjuvant Temozolomide in Patients With Glioblastoma Multiforme
Protocole ID MUHC ID: 4315 (M-HARTT STUDY)
ClinicalTrials.gov ID NCT02780024
Type(s) de cancer Cerveau (SNC)
Phase Phase II
      1001 boul. Décarie , Montréal, QC, H4A 3J1
Ville Montréal
Investigateur(trice) principal(e) Dr George Shenouda
Coordonnateur(trice) Marianna Perna
 514-934-1934 poste 43191
Statut Actif en recrutement
Critètes d'éligibilité
  • 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
Critètes d'exclusion
  • 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