Symptoms and General Pathology

All Conditions

Neoplasms

Nervous System Diseases

Diseases and Abnormalities at or Before Birth

Ear, Nose, and Throat Diseases

Skin and Connective Tissue Diseases

Rare Diseases

Recurrence

Neurilemmoma

Brain Neoplasms

Meningioma

Neurofibromatoses

Neurofibromatosis 1

Neurofibroma

Ependymoma

Neuroma, Acoustic

Neurofibromatosis 2

Solitary Fibrous Tumors

Hemangiopericytoma

Neoplasms, Fibrous Tissue

Neuroma

Disease Attributes

Central Nervous System Neoplasms

Nervous System Neoplasms

Neoplasms, Nerve Tissue

Neoplasms by Histologic Type

Neoplasms, Vascular Tissue

Meningeal Neoplasms

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Glandular and Epithelial

Nerve Sheath Neoplasms

Syndrome

Neoplastic Syndromes, Hereditary

Neurocutaneous Syndromes

Heredodegenerative Disorders, Nervous System

Neurodegenerative Diseases

Genetic Diseases, Inborn

Peripheral Nervous System Diseases

Neuromuscular Diseases

Peripheral Nervous System Neoplasms

Neuroendocrine Tumors

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Vestibulocochlear Nerve Diseases

Retrocochlear Diseases

Ear Diseases

Otorhinolaryngologic Diseases

Otorhinolaryngologic Neoplasms

Cranial Nerve Diseases

Schwannoma

Brain Tumor, Adult

Neurofibromatosis

Neurofibromatosis Type 1

Acoustic Neuroma

Neurofibromatosis Type 2

Neuroepithelioma

Neuroendocrine Tumor

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Bevacizumab

Immunoglobulins

Antineoplastic Agents, Immunological

Immunoglobulins, Intravenous

Angiogenesis Inhibitors

Growth Inhibitors

Immunologic Factors

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.

bevacizumab

Priya Kumthekar, MD

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.

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.

Bevacizumab in Treating Patients With Recurrent or Progressive Meningiomas

Phase II Trial of Bevacizumab in Patients With Recurrent or Progressive Meningiomas

Progression Free Survival (PFS) of patients with recurrent or progressive benign and atypical/malignant Meningiomas (grades I-III), despite prior therapy treated with bevacizumab will be defined from the time of registration to the study until the time of first documentation of progressive disease or death from any cause. Progressive disease will be assessed based on the Macdonald Criteria and is defined as 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, or clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR clear worsening or failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).

Best Response of patients treated with bevacizumab with diagnosis of any of the following: meningioma, hemangiopericytoma, hemangioblastoma, acustic neuroma or schwanoma will be assessed using the MacDonald Criteria.

In general:

Complete Response-Complete disappearance of all measurable and evaluable disease. No new lesions. No evidence of non-evaluable disease. Patients not on steroids.

Partial Response-50% or greater decrease under baseline in the sum of products of perpendicular diameters of the two largest measurable lesions. No progression of evaluable disease. No new lesions.

Stable Disease-Not CR or PR or PD. Progressive disease (PD)-25% increase in the sum of products of all measurable lesions over smallest sum observed, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR clear worsening or failure to return for evaluation due to death/deteriorating condition

Safety of bevacizumab in patients with diagnosis of any of the following: meningioma, hemangiopericytoma, hemangioblastoma, acustic neuroma or schwanoma, will be assessed by collecting the number of adverse events experienced by patients that were determined to be at least possibly related to bevacaumab and assessed as a grade 3 or 4. AEs will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.0.

In general, AEs will be graded as follows:

Grade 1 - Mild Grade 2 - Moderate Grade 3 - Severe Grade 4 - Life-threatening Grade 5 - Fatal

Tissue was collected for VEGF, VEGRfR2 and HER2 at baseline. Patients underwent radiological assessments every 8 weeks during treatment to determine disease status to treatment (complete response/partial response/stable disease/progressive disease). The level of VEGF, VEGRfR2 and HER2 marker expression was compared with the response as determined at the time of disease progression or death. Immunohistochemistry (IHC) will be analyzed using blobfinder technology.

Each sample was given a score for the markers expression in the tissue 1, 2 or 3 (1=+, 2=++, 3=+++, from low to high) and a percentage 0-100% (low to high) of how much tissue it was expressed in.

If score = 0 and percentage =0 the sample was negative for that marker. If score = 1 and percentage =10% the marker had an expression of 1 (+) in 10 percent of the tissue and so forth.

The data is shown by patient and their best response to treatment with their score and expression for VEGF, VEGRfR2 and HER2.

Overall Survival (OS) of patients with Recurrent or Progressive Meningiomas Treated with Bevacizumab will be measured from the time of treatment initiation to the study until death from any cause. The raw data of number of patients documented as being alive at 1 year, 2 year, and 3 years post treatment initiation is reported here.

Northwestern University

Data that has been collected in the database is reported here. There is still some data entry of other adverse events for a few patient being completed and this Section will be updated accordingly when all data is entered and available for reporting (if applicable).

Patients receive bevacizumab IV over 30-90 minutes every 2 weeks for 6 months (1 cycle = 28 days with two doses of bevacizumab). Patients may then receive bevacizumab IV every 3 weeks for up to 12 months (1 cycle = 42 days) or stay on the 2 week cycle at the discretion of the treating physician. Treatment continues in the absence of disease progression or unacceptable toxicity. After 12 months of treatment patients may continue on bevacizumab at the discretion of their treating physician.

bevacizumab: Given IV

Treatment With Bevacizumab

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Grading of disease was based on the degree of anaplasia, number of mitosis, and presence of necrosis using World Health Organization (WHO) classification of tumors of the central nervous system. Grades in general are as follows:

Grade I - Benign Grade II - Atypical Grade III - Malignant

Stage of Disease (at study entry)

Diagnosis

Grade I Meningioma

Grade II Meningioma

Grade III Meningioma

Grade II/III Meningioma

PFS was analyzed based on grading of meningioma due to the difference in prognosis of grades to provide meaningful results. In general, grade I tumor grows slowly, grade II tumor grows more quickly and is often called atypical meningioma, and grade III tumor grows and spreads very quickly and is often called anaplastic or malignant meningioma.

Progression Free Survival (PFS) of Patients With Recurrent or Progressive Meningiomas Treated With Bevacizumab at 6 Months

Number of Patients With Each Response

Hypertension

Hyponatremia

Proteinuria

Ataxia

Pancreatitis

Nausea/Vomiting

Elevated Lipase

Anemia

Infection

Muscle weakness

Epistaxis (Nosebleed)

Thrombus/embolism

Fatigue

Safety Profile of Bevacizumab

#01/Partial Response : VEGF Score

#01/Partial Response : VEGF Expression

#01/Partial Response : VEGRfR2 Score

#01/Partial Response : VEGRfR2 Expression

#01/Partial Response : HER2 Score

#01/Partial Response : HER2 Expression

#02/Stable Disease : VEGF Score

#02/Stable Disease : VEGF Expression

#02/Stable Disease : VEGRfR2 Score

#02/Stable Disease : VEGRfR2 Expression

#02/Stable Disease : HER2 Score

#02/Stable Disease : HER2 Expression

#03/Stable Disease : VEGF Score

#03/Stable Disease : VEGF Expression

#03/Stable Disease : VEGRfR2 Score

#03/Stable Disease : VEGRfR2 Expression

#03/Stable Disease : HER2 Score

#03/Stable Disease : HER2 Expression

#04/Stable Disease : VEGF Score

#04/Stable Disease : VEGF Expression

#04/Stable Disease : VEGRfR2 Score

#04/Stable Disease : VEGRfR2 Expression

#04/Stable Disease : HER2 Score

#04/Stable Disease : HER2 Expression

#07/Stable Disease : VEGF Score

#07/Stable Disease : VEGF Expression

#07/Stable Disease : VEGRfR2 Score

#07/Stable Disease : VEGRfR2 Expression

#07/Stable Disease : HER2 Score

#07/Stable Disease : HER2 Expression

#08/death : VEGF Score

#08/death : VEGF Expression

#08/death : VEGRfR2 Score

#08/death : VEGRfR2 Expression

#08/death : HER2 Score

#08/death : HER2 Expression

#09/Stable Disease : VEGF Score

#09/Stable Disease : VEGF Expression

#09/Stable Disease : VEGRfR2 Score

#09/Stable Disease : VEGRfR2 Expression

#09/Stable Disease : HER2 Score

#09/Stable Disease : HER2 Expression

#10/Stable Disease : VEGF Score

#10/Stable Disease : VEGF Expression

#10/Stable Disease : VEGRfR2 Score

#10/Stable Disease : VEGRfR2 Expression

#10/Stable Disease : HER2 Score

#10/Stable Disease : HER2 Expression

#11a/Stable Disease : VEGF Score

#11a/Stable Disease : VEGF Expression

#11a/Stable Disease : VEGRfR2 Score

#11a/Stable Disease : VEGRfR2 Expression

#11a/Stable Disease : HER2 Score

#11a/Stable Disease : HER2 Expression

#12/Stable Disease : VEGF Score

#12/Stable Disease : VEGF Expression

#12/Stable Disease : VEGRfR2 Score

#12/Stable Disease : VEGRfR2 Expression

#12/Stable Disease : HER2 Score

#12/Stable Disease : HER2 Expression

#13/Stable Disease : VEGF Score

#13/Stable Disease : VEGF Expression

#13/Stable Disease : VEGRfR2 Score

#13/Stable Disease : VEGRfR2 Expression

#13/Stable Disease : HER2 Score

#13/Stable Disease : HER2 Expression

#15/Stable Disease : VEGF Score

#15/Stable Disease : VEGF Expression

#15/Stable Disease : VEGRfR2 Score

#15/Stable Disease : VEGRfR2 Expression

#15/Stable Disease : HER2 Score

#15/Stable Disease : HER2 Expression

#16/Progressive Disease : VEGF Score

#16/Progressive Disease : VEGF Expression

#16/Progressive Disease : VEGRfR2 Score

#16/Progressive Disease : VEGRfR2 Expression

#16/Progressive Disease : HER2 Score

#16/Progressive Disease : HER2 Expression

#17/Stable Disease : VEGF Score

#17/Stable Disease : VEGF Expression

#17/Stable Disease : VEGRfR2 Score

#17/Stable Disease : VEGRfR2 Expression

Levels of VEGF, VEGRfR2 and HER2 Expression in Tumor Tissue as Compared to Response

Spots Global Cancer Trial Database for Bevacizumab in Treating Patients With Recurrent or Progressive Meningiomas

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial