The outcome for children with high-grade gliomas and diffuse intrinsic brainstem gliomas remains poor despite the use of multi-modal therapy with surgery, radiation therapy and chemotherapy.

Novel therapies are needed to improve the outcome of these children. Recent studies have demonstrated very promising results of treatment with bevacizumab/irinotecan in patients with recurrent high grade gliomas. Based on these promising results, and the tolerability of the irinotecan and bevacizumab in children with recurrent CNS malignancies both anecdotally and in a study conducted by the Pediatric Brain Tumor Consortium, we have designed a novel study incorporating concurrent radiation therapy with bevacizumab ± temozolomide followed by bevacizumab, irinotecan ±temozolomide in patients with newly diagnosed high-grade gliomas and diffuse intrinsic pontine gliomas.

Inclusion Criteria:

• Patients must be ≥ 3 years of age and ≤ 30 years of age at the time of study entry.

• Diagnosis:

  • High-grade glioma;Patients must have had histologically verified anaplastic astrocytoma, glioblastoma multiforme or gliosarcoma.Patients with primary spinal cord tumors are eligible.
  • Diffuse intrinsic pontine glioma (DIPG) are eligible.

• Performance Level: Karnofsky ≥ 50% for patients > 10 years of age and Lansky ≥ 50 for patients ≤ 10 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.

• Prior Therapy: no prior anticancer therapy.

• Concomitant Medications: The use of steroids is permissible.

• Organ Function Requirements All patients must have adequate organ function as defined below.

  • Adequate Bone Marrow Function
  • Adequate Renal Function
  • Adequate Liver Function

• Adequate Blood Clotting Defined As: INR, Fibrinogen, and PTT < Grade 2

• Central nervous system function. Patients with seizures may be enrolled if the seizures are well-controlled with non-enzyme inducing anticonvulsants.

• Informed Consent. Patients and/or parents/legal guardians must have signed an informed consent.

Exclusion Criteria:

• Patients with metastatic disease (i.e. M+ disease, or disease anywhere other than primary site).
• Patients with evidence of a new intracranial hemorrhage that is larger than a punctate size on baseline MRI scan.
• Allergies: Patients with a history of allergic reaction to Chinese hamster ovary cell products, or other recombinant human antibodies.
• Pregnant or breast feeding women will not be entered on this study.
• Patients of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study.
• Infection: Patients who require IV antibiotics at time of enrollment, or who are currently receiving treatment for Clostridium difficile infection are excluded.
• Thrombosis: Patients must not have been previously diagnosed with a deep venous or arterial thrombosis (including pulmonary embolism), and must not have a known thrombophilic condition.
• Serious or Non-Healing Wounds
• Surgical Procedures: Patients who have had major surgery should not receive the first dose of bevacizumab until 28 days after major surgery.
• Patients with uncontrolled systemic hypertension.
• Proteinuria with a urine protein (albumin)/creatinine ratio of ≥1.0.