OZM-063: This phase II trial is trying to determine the benefit of adding Bevacizumab (an intravenous drug) to chemotherapy treatment with Vinblastine, in children and adolescents with low grade gliomasA Phase II, Open-Labeled, Multi-Center, Randomized Controlled Trial of Vinblastine +/- Bevacizumab for the Treatment of Chemotherapy-Naïve Children With Unresectable or Progressive Low Grade Glioma (LGG)

Inclusion

1. Children and adolescents aged 6 months to < 18 years old with Low Grade Glioma (See Appendix I).
2. All patients must submit tumour tissue (fresh tumour tissue is recommended) and have pathological confirmation of LGG and determination of BRAF characteristics from the Hospital for Sick Children. Exceptions will be made for patients with neurofibromatosis type 1 who have not previously had a biopsy. NF1 patients are eligible without tissue confirmation but must have definitive clinical or radiographic evidence of tumour progression or risk for significant neurologic deterioration requiring immediate therapy. If a tissue sample for NF1 patients is available from a previous biopsy, it is required to be submitted for Central Review at the Hospital for Sick Children. Please refer to the lab manual for further details.
3. Patients must have progressive disease following surgical excision based on clear radiological or clinical evidence of progression, or an incomplete excision (< 95% or > 1.0 cm2 residual tumour) with necessity to begin treatment because of a risk of neurological impairment with progression.
4. All patients on study must have measurable tumour (>1.0 cm2 of residual tissue if resection has been performed) within 28 days of enrollment.
5. Patients must have received no prior therapy including chemotherapy, biological modifiers and/or radiation treatment for the tumour with the exception of surgery.
6. Patient is able to start treatment within 14 working days after randomization.
7. Post pubertal teenagers who are sexually active agree to use two methods of contraception during the treatment period and for at least 6 months after the last dose of study drug. Please refer to Appendix V for a list of acceptable methods of contraception.
8. Lansky performance status > 50% for patients < 16 years of age. Karnofsky performance status > 50% for patients ≥ 16 years of age.
9. Patients with neurologic deficits must have deficits that are stable for a minimum of 1 week prior to enrollment.
10. Patients receiving corticosteroids must be on a stable or decreasing dose for at least 1 week prior to enrollment.
11. Life expectancy > 2 months at the time of enrollment.
12. Parents/guardians must provide written informed consent and to agree that they (and the patient) will comply with the study protocol.
13. Written assent by patient according to institutional guidelines.

14. Patients must have adequate bone marrow function within 2 weeks prior to enrollment:

    • Hemoglobin ≥ 10 g/dL (may be supported )
    • Neutrophil count ≥ 1.0 × 109/L
    • Platelet count ≥ 100 × 109/L (transfusion independent)
15. Patients not on a therapeutic dose of an anti-coagulant must have an INR ≤ 1.5 and an aPTT ≤ 1.5x institutional ULN for age within 2 weeks prior to enrollment. Anti-coagulation is permitted prior to enrollment on the condition that the patient is, according to the local clinical practice guidelines or approved product labeling, adequately anti-coagulated prior to enrollment.

16. Patients must have satisfactory liver function within 2 weeks prior to enrollment:

    • AST ≤ 3x institutional ULN for age
    • ALT ≤ 3x institutional ULN for age
    • Total Bilirubin ≤ 1.5x institutional ULN for age

17. Patients must have satisfactory renal parameters and meet the following criteria within 2 weeks prior to enrollment :

    • Serum creatinine must be ≤ 1.5x ULN for age. If the serum creatinine is > 1.5 × ULN, the glomerular filtration rate (either estimated or formal) must be >90 mL/min/1.73 m2, for patient to be enrolled.
    • Absence of clinically significant proteinuria, as defined by screening of the early morning urine (urine protein < 1g/L and/or albumin/creatinine ratio < 1.0 (mg/mmol)). If urine protein ≥ 1g/L, then Urine Protein Creatinine (UPC) ratio should be calculated. If UPC ratio > 0.5, 24-hour urine protein should be obtained and the level should be < 1000 mg/24 hours for patient enrollment. Note: UPC ratio of spot urine is an estimation of the 24 urine protein excretion - a UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1 g. UPC ratio is calculated using one of the following formulas:

[urine protein]/[urine creatinine] - if both protein and creatinine are reported in mg/dL or [(urine protein) x0.088]/[urine creatinine] - if urine creatinine is reported in mmol/L

Quality of Life Correlative Study Inclusion Criteria (Optional):

1. Age ≥ 3 and < 18 years.
2. English- or Spanish-speaking.
3. No known history of a significant neurodevelopmental disorder prior to diagnosis of LGG (e.g., Down syndrome, Fragile X, William's Syndrome, mental retardation). Patients with NF1 are not excluded.
4. No significant motor or sensory impairment that would prevent computer use and perception of the visual and auditory test stimuli.