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

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)