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 \< 6 months of age)
  * 0.5 mg/dL (6 months to \< 1 year of age)
  * 0.6 mg/dL (1 to \< 2 years of age)
  * 0.8 mg/dL (2 to \< 6 years of age)
  * 1.0 mg/dL (6 to \< 10 years of age)
  * 1.2 mg/dL (10 to \< 13 years of age)
  * 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to \< 16 years of age)
  * 1.7 mg/dL (male) or 1.4 mg/dL (female) (≥ 16 years of age)
* Proteinuria \< 2+ OR urine; protein ratio (UPC) ≤ 0.5

  * If UPC \> 0.5, a 24-hour urine protein should be obtained and level should be \< 1,000 mg of protein
* Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
* ALT \< 2.5 times ULN
* Serum albumin ≥ 2 g/dL
* PT INR ≤ 1.5 times ULN
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during all study therapy and for ≥ 6 months after completion of bevacizumab
* Hypertension well controlled (≤ 95\^th percentile for age and height if patient is ≤ 17years) by stable doses of medication allowed

  * For patients \> 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