Open-label, Phase 2 Study of Bevacizumab in Children and Young Adults With Neurofibromatosis 2 and Progressive Vestibular Schwannomas That Are Poor Candidates for Standard Treatment With Surgery or Radiation

• Patients must have a confirmed diagnosis of neurofibromatosis 2 by fulfilling National Institute of Health (NIH) criteria or Manchester criteria, or by detection of a causative mutation in the Neurofibromatosis 2 (NF2) gene.

• Patients must have measurable disease, defined as at least one VS \> 1.0 ml (on volumetric analysis) that can be accurately measured by contrast-enhanced cranial MRI scan with fine cuts through the internal auditory canal (3 mm slices, no skip).

• Age 6 years or greater (no upper limit) on day 1 of treatment. Given the potential risk of long-term bevacizumab use, children under age 6 are not eligible for treatment. No upper limit for adults.

• Life expectancy of greater than 1 year.

• Karnofsky performance status ≥ 70.

• Participants must have normal organ and marrow function as defined below with definitions micro liter (mcL), Aspartate aminotransferase (AST), Serum glutamic oxaloacetic transaminase (SGOT), Alanine aminotransferase (ALT), Serum glutamic pyruvic transaminase (SGPT):

• Leukocytes \> 3,000/mcL

• Absolute neutrophil count \> 1,500/mcL

• Platelets \> 100,000/mcL

• Total bilirubin within normal institutional limits

• AST (SGOT)/ALT (SGPT) \< 2.5 X institutional upper limit of normal

• Patients must have a creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥60ml/min/1.73 m2 or a normal serum creatinine based on age described in the table below:

• Age Maximum Serum Creatinine (mg/dL) 6 to \< 10 years 1(Male) 1(Female) 10 to \< 13 years 1.2(Male) 1.2(Female) 13 to \< 16 years 1.5(Male) 1.4(Female

• ≥ 16 years 1.7(Male) 1.4(Female)

• Subjects must have a target VS with the following qualities:

• Not amenable to surgery due to patient refusal, high risk for surgical complications (e.g., damage to lower cranial nerve function, tumor size \> 3 cm in longest diameter, or multilobulated tumor appearance on MRI scan).

• Associated with a word recognition score of \< 85%

• Documented clinical progression defined as EITHER:

• Progressive hearing loss (defined as a decline in word recognition score below the 95% critical difference interval from baseline score \[Appendix A\] related to VS (i.e., not due to prior interventions such as surgery or radiation)

⁃ OR

• Progressive tumor growth in the preceding 18 months, defined as ≥ 20% increase in volume

• The effects of bevacizumab on the developing human fetus are unknown. For this reason and because bevacizumab agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

• Ability to understand and the willingness to sign written informed consent and assent documents.

• Must have established relationship with primary care physician and provide contact information