Bevacizumab for Symptomatic Vestibular Schwannoma in Neurofibromatosis Type 2 (NF2)

Inclusion Criteria

• 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 NF2 gene
• The NIH criteria (82) includes presence of:
• Bilateral vestibular schwannomas, OR
• First-degree relative with NF2 and EITHER unilateral eighth nerve mass OR two of the following: neurofibroma, meningioma, glioma, schwannoma, juvenile posterior subcapsular lenticular opacity
• The Manchester criteria (101) includes presence of:
• Bilateral vestibular schwannomas, OR
• First-degree relative with NF2 and EITHER unilateral eighth nerve mass OR two of the following: neurofibroma, meningioma, glioma, schwannoma, juvenile posterior subcapsular lenticular opacity, OR
• Unilateral vestibular schwannoma AND any two of: neurofibroma, meningioma, glioma, schwannoma, juvenile posterior subcapsular lenticular opacity, OR
• Multiple meningiomas (two or more) AND unilateral vestibular schwannoma OR any two of: schwannoma, glioma, neurofibroma, cataract
• Patients must have measurable disease, defined as at least one VS >= 1.5 cm (on longest diameter) as measured by contrast-enhanced cranial MRI scan with fine cuts through the internal auditory canal (3 mm slices, no skip)
• Life expectancy of greater than 6 months
• ECOG performance status (Karnofsky >= 60% or Lansky Score >= 60)
• Patients must have normal organ and marrow function as defined below:
• Leukocytes >= 3,000/mcL
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 150, 000/mcL or lower limit of institutional normal
• Total bilirubin = = 60ml/min/1.73 m^2 or a normal serum creatinine based on age described in the table below:
• Age(years) = 15: 1.5 mg/dL
• Subjects must have a VS not amenable to surgery or have refused surgery due to high risk for permanent complications related to surgery (e.g. damage to lower cranial nerve function, facial palsy, risk for cerebrospinal fluid leak, etc.) as determined by a surgeon with experience in management of NF2 associated VS
• Subjects must have had a discussion of all available treatment options and their risks and benefits of these options including surgery, radiation therapy, observation, other clinical trials and expressed their preference for participation in this trial in the informed consent process
• The effects of bevacizumab on the developing human fetus at the recommended therapeutic dose are unknown; for this reason and because anti-angiogenic 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 give written informed consent or assent
• Evidence of active disease, defined as progressive hearing loss (with decrease in word recognition score) related to VS (i.e., not due to prior interventions such as surgery or radiation) documented in the preceding 24 months with a word recognition score of 160 mmHg and/or DBP > 90 mmHg despite antihypertensive medication, pediatric subjects: Requirement for antihypertensive treatment prior to enrollment, or diastolic blood pressure > 95th percentile for age)
• History of CVA within 12 months
• Myocardial infarction or unstable angina within 12 months
• New York heart association grade II or greater congestive heart failure
• Serious and inadequately controlled cardiac arrhythmia
• Significant vascular disease (e.g. aortic aneurysm, history of aortic dissection)
• Clinically significant peripheral vascular disease
• Pregnant women (positive pregnancy test) are excluded from this study because bevacizumab is an anti-angiogenic agent with the potential for teratogenic or abortifacient effects;