Protective VEGF Inhibition for Isotoxic Dose Escalation in Glioblastoma

Inclusion Criteria: * IDH wild-type, MGMT unmethylated glioblastoma patients * Informed consent * Age ≥18 and ≤70 years, smoking or non-smoking, of any ethnic origin * ECOG 0-2 * Neutrophil counts \>1500/µl, Platelet counts \>100.000/µl, Hemoglobin \> 8 g/dl, Serum creatinine \<1.5-fold upper limit of normal (ULN), Bilirubin, AST or ALT \<2.5-fold ULN unless attributed to anticonvulsants, Alkaline phosphatase \<2.5-fold ULN * Adequate contraception * Serum creatinine ≤ 1.5 x ULN AND patients with urine dipstick for proteinuria \< 2+. Patients with ≥ 2+ proteinuria on dipstick urinalysis at baseline should show urine protein to creatinine ratio ≤ 1 Exclusion Criteria: * Evidence of significant hemorrhage on postoperative MRI of the brain. Patients with asymptomatic, minor hemosiderin deposition, resolving postsurgical hemorrhagic changes, or punctate intratumoral hemorrhage (e.g., related to biopsy or surgery) are not excluded * Subjects on any drug suspected to interfere with bevacizumab at the time of study inclusion * Immuno-compromised patients, including known seropositivity for human immunodeficiency virus (HIV) * Known hypersensitivity to any component of the investigational drugs or excipients (allergy to or other intolerability of bevacizumab or excipients) * Any other significant medical illness or medically significant laboratory finding that would, in the investigator's judgement, make the patient inappropriate for this study, or would increase the risk associat…