Vorinostat, Temozolomide, or Bevacizumab in Combination With Radiation Therapy Followed by Bevacizumab and Temozolomide in Young Patients With Newly Diagnosed High-Grade Glioma

Inclusion Criteria

• Newly diagnosed high-grade glioma
• Anaplastic astrocytoma
• Glioblastomamultiforme
• Gliosarcoma
• Primary spinal cord malignant glioma allowed
• No oligodendroglioma oroligoastrocytoma
• Patient must have histological verification of diagnosis
• No M+ disease (defined as evidence of neuraxis dissemination)
• No positive CSF cytology
• ECOG performance status (PS) 0-2
• Karnofsky PS 50-100% (patients > 16 years of age)
• Lansky PS 50-100% (patients ≤ 16 years of age)
• ANC ≥ 1,000/μL
• Platelet count ≥ 100,000/μL
• Hemoglobin ≥ 8.0 mg/dL (transfusion independent)
• Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR serum creatinine based on age and/or gender as follows:
• 0.4 mg/dL (1 month to 0.5, a 24-hour urine protein should be obtained and level should be 17 years, systolic blood pressure (BP) ≤ 150 mm Hg or diastolic BP ≤ 100 mm Hg)
• Seizure disorder allowed provided patient is well-controlled and on nonenzyme-inducing anticonvulsants
• No history of myocardial infarction, severe or unstable angina, clinically significant peripheral vascular disease, ≥ grade 2 heart failure, or serious and inadequately controlled cardiac arrhythmia
• No known bleeding diathesis or coagulopathy
• No prior arterial thromboembolic events, including transient ischemic attacks orcerebrovascular accidents
• No prior diagnosis of a deep venous thrombosis, including pulmonary embolism, and no known thrombophilic condition (e.g., protein S, protein C, antithrombin III deficiency, Factor V Leiden or Factor II G202'0A mutation, homocysteinemia, or antiphospholipid antibody syndrome)
• No history of an abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
• No serious or non-healing wound, ulcer, or bone fracture
• No evidence of significant postoperative intracranial hemorrhage, defined as > 1 cm of blood on postoperative MRI scan (potentially in addition to the postoperative scan) obtained within the past 14days
• No history of allergic reaction to Chinese hamster ovary cell products or other recombinanthuman antibodies
• No more than 31 days since definitive surgery
• Must not have received any prior chemotherapy, radiotherapy, immunotherapy, or bone marrow transplant
• More than 7 days since major surgical procedure and recovered
• For patients scheduled to receive bevacizumab:
• More than 28 days since major procedure
• More than 14 days since intermediate procedure
• More than 7 days since minor procedure (lumbar picture or placement of PICC lines are not considered minor procedures)
• No other current anti-cancer agents
• No concurrent nonsteroidal anti-inflammatory medications known to inhibit platelet function or known to selectively inhibit cyclooxygenase activity
• No concurrent enzyme inducing anticonvulsants
• No concurrent HDAC inhibitors (e.g., valproic acid)
• No concurrent anticoagulants including systemic thrombolytic agents, heparin, low molecular weight heparins, or warfarin except as required to maintain patency of pre-existing permanent vascular catheters or for prevention of thrombosis in the post-operative period