Bevacizumab in Treating Patients With Recurrent or Progressive Meningiomas

Northwestern University

Status and phase

Completed

Phase 2

Conditions

Adult Grade II Meningioma

Neurofibromatosis Type 1

Adult Meningeal Hemangiopericytoma

Adult Anaplastic Meningioma

Recurrent Adult Brain Tumor

Adult Grade I Meningioma

Neurofibromatosis Type 2

Adult Papillary Meningioma

Acoustic Schwannoma

Adult Ependymoma

Treatments

Biological: bevacizumab

Study type

Interventional

Funder types

Other

Identifiers

NCT01125046

NU 09C2

STU00024715 (Other Identifier)

NCI-2010-00843

Details and patient eligibility

About

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.

Full description

PRIMARY OBJECTIVES:

I. To determine the efficacy of bevacizumab in patients with recurrent or progressive benign and atypical/malignant meningiomas, despite prior therapy, as measured by six-month progression-free survival.

SECONDARY OBJECTIVES:

I. To describe the response rate and overall-survival in this patient population.

II. To evaluate the safety profile of bevacizumab in patients with recurrent meningiomas.

III. To perform an exploratory study in patients with hemangioblastoma and hemangiopericytoma.

IV. To assess tissue for VEGF and VEGFR to correlate with response. An exploratory analysis of HER-2 will be performed.

OUTLINE:

Patients receive bevacizumab IV over 30-90 minutes every 2 weeks for 6 months. Patients may then receive bevacizumab IV every 3 weeks for up to 12 months. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 2 years.

Enrollment

50 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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