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

People who have neurofibromatosis type 2 (NF2) can have tumors that grow on the auditory nerves and cause hearing loss. These tumors are called vestibular schwannomas (VSs), or acoustic neuromas. People with NF2 can also get schwannomas in other parts of their body, as well as tumors called meningiomas and ependymomas. Because VSs can cause hearing loss, many people with NF2 will have treatment to preserve their hearing. This treatment usually involves surgery. Because surgery has risks and is not able to help everyone with VSs, other methods of treatment are being explored. One area of exploration is looking to see if there is a drug that can be taken that might prevent the VSs from growing larger and causing hearing loss or brainstem compression. This study is exploring whether a drug that is approved by the FDA and is currently used to treat other tumors might also work to treat VSs. Based on people who have taken this drug to treat VSs already, there is some reason to think that it might be helpful to certain people with NF2. People enrolled in this study will receive the drug one time every three weeks for one year by infusion. This study will follow subjects over the course of the year that the person is taking the drug and for six months after the drug is stopped. This study is recruiting people who have NF2 and are currently having symptoms of tinnitus, dizziness, and/or hearing loss from their VSs. If you have NF2 and are currently having symptoms caused by your VSs, you may be eligible to participate.

PRIMARY OBJECTIVES:

I. The primary objective of this study is to determine the activity of bevacizumab for treatment of symptomatic vestibular schwannomas (VS) defined as progressive hearing loss in patients with neurofibromatosis type 2 (NF2) based on objective hearing response.

SECONDARY OJBECTIVES:

I. Determine the safety and tolerability of bevacizumab in this patient population on an every three week dosing schedule of 7.5mg/kg for 12 months of therapy.

II. Assess the rate of radiographic response (\>= 20% reduction in volume). III. Determine the growth rate of VS using volumetric MRI analysis in comparison to 1-dimensional and 2-dimensional measurements.

IV. Assess changes in function of the auditory system during bevacizumab treatment.

V. Assess the vascular permeability (Ktrans), relative cerebral blood volume/flow, mean transit time, and mean vessel diameter from perfusion-weighted MRI.

VI. Assess the change in circulating endothelial cells, circulating progenitor cells, and plasma angiogenic proteins in subjects receiving bevacizumab treatment.

VII. Observe the impact of bevacizumab on non-VS tumors in patients with NF2 via whole body MRI.

VIII. Explore hearing related QOL measures throughout treatment. IX. Explore the effect of treatment with bevacizumab on auditory function using distortion product optoacoustic emissions (DPOAE) (to be evaluated at NCI only).

OUTLINE:

Patients receive bevacizumab intravenously (IV) over 30-90 minutes once every 3 weeks. Courses repeat every 6 weeks for up to 48 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 3 and 6 months.

Eligibility Criteria:
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 =\< 2 X institutional upper limit of normal
* AST(SGOT)/ALT(SGPT) =\< 2.5 X institutional upper limit of normal
* Patients must have recovered from acute toxicity of prior treatment to grade 1 or less unless otherwise specified
* Patients must have a creatinine clearance or radioisotope GFR \>= 60ml/min/1.73 m\^2 or a normal serum creatinine based on age described in the table below:

  * Age(years) =\< 5: 0.8 mg/dL
  * 5 \< age (years) =\< 10: 1.0 mg/dL
  * 10 \< age (years) =\< 15: 1.2 mg/dL
  * 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 \< 90% in the target ear
* Proteinuria (including albuminuria) should be screened for by either urine analysis for urine protein creatinine (UPC) ratio or by urine dipstick; if the UPC ratio is greater than or equal to 0.5 or if urine dipstick shows 2+ proteinuria, 24-hour urine protein should be obtained and the level should be \< 1000 mg for patient enrollment

Exclusion Criteria:

* Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
* Patients may not be receiving any other investigational agents
* Patients with nervous system tumors associated with NF2 (e.g., schwannomas, meningiomas, ependymomas, or gliomas) will not be excluded from this clinical trial as long as these tumors do not require treatment with radiation, surgery, or medical treatment at the time of enrollment on trial
* Patients with known hypersensitivity of Chinese hamster ovary cell products, other recombinant human antibodies, or compounds of similar chemical or biologic composition to bevacizumab
* Inability to tolerate periodic MRI scans or gadolinium contrast without general anesthesia
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements
* Clinically significant cardiovascular disease, such as:

  * Inadequately controlled HTN (adult subjects: SBP \> 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; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with bevacizumab, breastfeeding should be discontinued if the mother is treated with bevacizumab; both fertile men and women must agree to use adequate contraceptive measures during study therapy and for at least 6 months after the completion of bevacizumab therapy; abstinence is considered an adequate contraceptive measure

  * In the event that a minor (age 12-17) who undergoes a pregnancy test as part of the screening process receives a positive result, they will be excluded from the study and their parent(s) of record will be notified of this result
* HIV-positive patients or cancer survivors are eligible for this study if they fulfill all other eligibility criteria
* Inability to perform volumetric measurement of target VS (e.g., due to the MRI artifact from auditory brainstem implant or due to presence of collision tumor (two or more tumors abutting each other) in the cerebellopontine angle); Note: questions about the ability to perform volumetric analysis on a baseline MRI scan should be directed to the study radiologist, Dr. Gregory Sorensen
* Concurrent use of anti-coagulant drugs (not including prophylactic doses), history of coagulopathy, or evidence of bleeding diathesis or coagulopathy
* Imaging (CT or MRI) evidence of newly identified hemorrhage (new within the last in the 6 months prior to enrollment), any history of symptomatic intracranial hemorrhage, or any history of spontaneous intracranial hemorrhage
* Serious or non-healing wound, ulcer or bone fracture
* History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to day 1
* Invasive procedures defined as follows:

  * Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to Day 1 therapy
  * Brain biopsy within 28 days prior to day 1 of therapy (wounds must be fully healed from brain biopsies performed more than 28 days prior to day 1 of therapy)
  * Anticipation of need for major surgical procedures during the course of the study
  * Core biopsy within 7 days prior to D1 therapy
* Prior treatment with bevacizumab or other VEGF targeting therapies
* Personal history of autoimmune coagulopathy, including idiopathic thrombocytopenia purpura (ITP)