Bevacizumab in Treating Patients With Recurrent or Progressive Meningiomas
Condition: Acoustic Schwannoma; Adult Anaplastic Meningioma; Adult Ependymoma; Adult Grade I Meningioma; Adult Grade II Meningioma; Adult Meningeal Hemangiopericytoma; Adult Papillary Meningioma; Neurofibromatosis Type 1; Neurofibromatosis Type 2; Recurrent Adult Brain Tumor
MeSH terms: Meningioma; Ependymoma; Neurofibromatoses; Neurofibromatosis 1; Neurofibroma; Neurilemmoma; Hemangiopericytoma; Solitary Fibrous Tumors; Neurofibromatosis 2; Neuroma, Acoustic; Recurrence
Intervention: bevacizumab
Intervention description: Given IV
Intervention MeSH terms: Bevacizumab; Antineoplastic Agents, Immunological; Antibodies; Immunoglobulins; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different
      ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and
      help kill them or carry tumor-killing substances to them.

      PURPOSE: This phase II trial is studying how well bevacizumab works in treating patients with
      recurrent or progression meningiomas.
    

Eligibility criteria:

        Criteria

          -  Histologically proven recurrent or progressive intracranial meningioma; this includes
             benign, atypical, or malignant meningioma who may or may not have neurofibromatosis
             type 1 or 2; pathology can be from initial surgery; OR histologically proven
             intracranial hemangiopericytoma, hemangioblastoma (with or without metastatic
             disease), acoustic neuroma, or intracranial schwannoma

          -  Unequivocal evidence for tumor progression by MRI (or CT scan if MRI is
             contraindicated); the scan must be performed within 14 days of registration

          -  Steroid dosing- must be on stable dose for at least 5 days prior to baseline imaging
             (Steroids are not required at the time of baseline imaging)

          -  Recent resection for recurrent tumor - patients will be eligible as long as they are
             greater than four weeks from surgery, have recovered from the effects of surgery, and
             have residual disease that can be evaluated; to best assess the extent of residual
             disease post-operatively, a CT/MRI should be done no later than 96 hours in the
             immediate post-operative period or at least 4 weeks post-operatively; if the 96 hour
             scan is more than 14 days before registration, it should be repeated

          -  Prior radiation therapy - patients may have been treated with standard external beam
             radiation or radiosurgery in any combination; an interval of >= 8 weeks (56 days) must
             have elapsed from the completion of radiation therapy to study entry and there must be
             subsequent evidence of tumor progression

          -  Patients with prior stereotactic radiosurgery must have confirmation of true
             progressive disease rather than radiation necrosis based on PET, MR spectroscopy or
             surgical documentation of disease

          -  Prior therapy: there is no limitation on the number of prior surgeries, radiation
             therapy, radiosurgery treatments, or chemotherapy agents

          -  Prior surgery: must be > 4 weeks from surgery

          -  Prior radiation: must be 8 weeks from end of treatment

          -  Prior chemotherapy: must be at least 4 weeks from cytotoxic therapy and 2 weeks from
             biologic therapies

          -  All patients must sign an informed consent indicating that they are aware of the
             investigational nature of the study

          -  Patients must sign an authorization for the release of their protected health
             information

          -  Karnofsky performance status >= 60%

          -  Absolute neutrophil count (ANC) >= 1,000/mm^3

          -  Platelets >= 100,000/mm^3

          -  Hemoglobin >= 8gm/dl

          -  Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase [SGOT]) =<
             2.5 x local laboratory upper limit of normal (ULN)

          -  Serum alanine transaminase (ALT; serum glutamic pyruvic transaminase [SGPT]) =< 2.5 x
             local laboratory upper limit of normal (ULN)

          -  Creatinine =< 2.0 mg/dl

          -  PT, INR, and PTT =< 1.5 times institutional upper limits of normal

          -  Total serum bilirubin =< 1.5

          -  Patients with a history of NF may have other stable CNS tumors, such as schwannoma,
             acoustic neuroma, or ependymoma, but ONLY if these lesions have been stable in size
             for the preceding 6 months

          -  No history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ
             of the cervix) unless in complete remission and off all therapy for the disease for a
             minimum of 5 years

          -  Patients may not have a history of prior treatment with inhibitors of the VEGF pathway
             (eg: VEGF trap, cediranib, vatalanib, sunitinib, sorafenib, etc.)

          -  No concurrent treatment on another clinical trial; supportive care trials or
             non-treatment trials, e.g. QOL, are allowed

          -  No history of known human immunodeficiency virus (HIV) or acquired immunodeficiency
             syndrome (AIDS)-related illness or other active infection

          -  Anticoagulation with therapeutic warfarin (INR <3) and low molecular weight heparin is
             allowed

          -  Pregnancy or breast-feeding (Patients must be surgically sterile, postmenopausal, or
             agree to use effective contraception during the period of therapy; the definition of
             effective contraception will be based on the judgment of the principal investigator or
             a designated associate)

          -  Male patients must be surgically sterile or agree to use effective contraception;
             women of childbearing potential must have a negative B-HCG pregnancy test documented
             within 14 days prior to registration

          -  Patient must be able to comply with the study and follow-up procedures

          -  Life expectancy greater than 12 weeks

          -  Adequately controlled hypertension (defined as systolic blood pressure =< 150 mmHg
             and/or diastolic blood pressure =< 100 mmHg)

          -  No history of hypertensive crisis or hypertensive encephalopathy

          -  Patients must not have New York Heart Association (NYHA) Grade II or greater
             congestive heart failure

          -  No history of myocardial infarction or unstable angina within 12 months prior to Day 1
             of treatment

          -  No history of stroke or transient ischemic attack

          -  Patients must not have significant vascular disease (e.g., aortic aneurysm, requiring
             surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day
             1 of treatment

          -  No history of hemoptysis (>= 1/2 teaspoon of bright red blood per episode) within 1
             month prior to Day 1 of treatment

          -  No evidence of bleeding diathesis or significant coagulopathy (in the absence of
             therapeutic anticoagulation)

          -  No history of major surgical procedure, open biopsy, or significant traumatic injury
             within 28 days prior to Day 1 of treatment or anticipation of need for major surgical
             procedure during the course of the study

          -  No history of minor surgical procedure, excluding placement of a vascular access
             device, within 7 days prior to Day 1 of treatment

          -  No history of abdominal fistula or gastrointestinal perforation within 6 months prior
             to Day 1 of treatment

          -  Patients must not have serious non-healing wound, active ulcer, or unhealed bone
             fracture

          -  Urine protein:creatinine (UPC) ratio =< 1.0 at screening OR urine dipstick for
             proteinuria < 2 (patients discovered to have >= 2 proteinuria on dipstick urinalysis
             at baseline should undergo a 24 hour urine collection and must demonstrate =< 1g of
             protein in 24 hours to be eligible)

          -  No known hypersensitivity to any component of bevacizumab

          -  Patients may not have a prior history of bowel perforation