Bevacizumab in Treating Patients With Recurrent or Progressive Meningiomas

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Northwestern University
ClinicalTrials.gov Identifier:
NCT01125046
First received: May 7, 2010
Last updated: September 26, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
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
Biological: bevacizumab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Bevacizumab in Patients With Recurrent or Progressive Meningiomas

Resource links provided by NLM:


Further study details as provided by Northwestern University:

Primary Outcome Measures:
  • Progression free survival [ Time Frame: At 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Response rate and overall-survival [ Time Frame: During week 8, every 8 weeks thereafter while on treatment and intermittently during followup ] [ Designated as safety issue: No ]
    Patients will have scans during week 8 and every 8 weeks thereafter while on treatment to assess response. Survival status will be confirmed intermittently during followup.

  • Safety profile of bevacizumab [ Time Frame: Every 2 weeks while on treatment up to 28 days after the last dose ] [ Designated as safety issue: Yes ]
    Adverse events will be assessed every 2 weeks while on treatment up to 28 days after the last dose.

  • Levels of VEGF and VEGFR expression in tumor tissue as compared to response rate [ Time Frame: At baseline and every 8 weeks until disease progression or death ] [ Designated as safety issue: No ]
    Tissue will be collected for the VEGF and VEGFR correlative studies during the screening phase. Patients will undergo radiological assessments every 8 weeks during treatment to determine disease status. The level of VEGF and VEGFR expression will be compared with the response rate as determined at the time of disease progression or death.


Estimated Enrollment: 50
Study Start Date: July 2010
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
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.
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • anti-VEGF rhuMAb
  • Avastin
  • recombinant humanized anti-VEGF monoclonal antibody
  • rhuMAb VEGF

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01125046

Locations
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
United States, Virginia
University of Virginia
Charlottesville, Virginia, United States, 22903
United States, Washington
University of Washington
Seattle, Washington, United States, 98109-1023
Sponsors and Collaborators
Northwestern University
Investigators
Principal Investigator: Priya Kumthekar, MD Northwestern University
  More Information

No publications provided

Responsible Party: Northwestern University
ClinicalTrials.gov Identifier: NCT01125046     History of Changes
Other Study ID Numbers: NU 09C2, NCI-2010-00843, STU00024715
Study First Received: May 7, 2010
Last Updated: September 26, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Neurofibromatoses
Neurofibromatosis 1
Neurofibromatosis 2
Brain Neoplasms
Ependymoma
Hemangiopericytoma
Meningioma
Neurilemmoma
Osteitis Fibrosa Cystica
Neuroma, Acoustic
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Vascular Tissue
Meningeal Neoplasms
Neuroendocrine Tumors
Nerve Sheath Neoplasms
Neuroma
Peripheral Nervous System Neoplasms

ClinicalTrials.gov processed this record on April 17, 2014