A Study of Low Dose Bevacizumab With Conventional Radiotherapy Alone in Diffuse Intrinsic Pontine Glioma

Inclusion Criteria:

1. Tumour Diagnosis: Newly diagnosed non-disseminated treatment naïve DIPG by classic clinical AND radiographic finding.
2. Age: Patient must be 3 to 18 years of age at the time of diagnosis.
3. Performance Score: KPS \> 12 y/o \>/= 50 or LPS for \< 12y \>/= 50 assessed at enrollment.
4. Participants must have normal organ and marrow function as defined below within two weeks prior to enrollment:

   1. Hematological: Absolute neutrophil count \> 1,000/mcL, Platelets\> 100,000/mcL (transfusion independent), HB \> 8gm/dL (can be transfused)
   2. Hepatic: Total bilirubin \< 1.5 times the upper limit of normal; alanine aminotransferase \[SGPT (ALT)\] and aspartate aminotransferase \[SGOT (AST)\] \< 5 times the institutional upper limit of normal.
   3. Renal: Serum creatinine which is less than 1.5x the upper limit of institutional normal for age or Glomerular Filtration Rate (GFR) \> 70 ml/min/1.73m2.; The absence of clinically significant proteinuria as defined by a screening early morning urine (first sample) dipstick urinalysis of \< 2.
   4. Normal coagulation profile
5. Post-Biopsy patients allowed, but should not have evidence of haemorrhage greater than 0.5cm intracranially and should satisfy this criterion within two to four weeks of biopsy to start treatment in Arm 1 if designated as per perfusion study along with satisfying other criteria as applicable. For arm 2, there will be no restriction other than the usual criteria.
6. No contra-indication for GA for MRI
7. Would not need GA for RT in the hypofractionated subgroup (due to logistics).
8. Ability to understand and the willingness to sign a written informed consent document by the parent or guardian and assent by the child as applicable and as per institutional policy.

Exclusion Criteria:

Other than those mentioned above,

1. Surgical Procedures: Patients who have had major surgery should not receive the first dose of BVZ until 28 days after major surgery or Serious or Non-Healing Wounds
2. Patients with uncontrolled systemic hypertension/ Proteinuria with a urine protein (albumin)/creatinine ratio of ≥1.0.
3. 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.
4. Allergies: Patients with a history of allergic reaction to Chinese hamster ovary cell products, or other recombinant human antibodies.