Ph 1/2 CTO With Lomustine for Bevacizumab-Naive Recurrent Glioma

Inclusion Criteria: * Phase 1 portion: Patients must have recurrent histologically confirmed diagnosis of WHO grade III or IV malignant glioma with no more than 3 prior progressions * Phase 2 portion: Patients must have recurrent histologically confirmed diagnosis of WHO grade IV malignant glioma (glioblastoma or gliosarcoma) with no more than 3 prior progressions * Patients should have received optimal surgical management and radiotherapy prior to study enrollment * Age ≥ 18 years * Karnofsky Performance Status (KPS) ≥ 70% * Bi-dimensionally measurable disease as assessed by magnetic resonance imaging based on RANO criteria * Absolute Neutrophil Count (ANC) ≥ 1000 cells/µl, Platelets ≥ 100,000 cells/µl (without transfusion within 14 days before enrollment) * Adequate renal function as indicated by the following: Serum creatinine \< 1.25 times upper limit of normal or calculated creatinine clearance ≥ 50 ml/minute and urine dipstick for proteinuria \< 2+ unless a 24-hour urine protein \<1 g of protein is demonstrated * Prothrombin time (PT) ≤ 1.5 x upper limit of normal (ULN) and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN within 14 days prior to first study treatment for patients not receiving anti-coagulation. The use of full-dose oral or parenteral anticoagulants is permitted as long as the PT or aPTT is within therapeutic limits (according to the medical standard of the enrolling institution) and the patient has been on a stable dose of anticoagulants for at…