Bevacizumab in Treating Patients With Recurrent or Progressive Meningiomas

Phase 2

Completed

• Conditions: Adult Grade I Meningioma; Adult Papillary Meningioma; Neurofibromatosis Type 2; Adult Ependymoma; Recurrent Adult Brain Tumor; Acoustic Schwannoma; Adult Meningeal Hemangiopericytoma; Neurofibromatosis Type 1; Adult Anaplastic Meningioma; Adult Grade II Meningioma
• Interventions: Biological: bevacizumab

• Registration Number: NCT01125046
• Lead Sponsor: Northwestern University

Brief 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.

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2010-05-07
• Study First Submitted QC: 2010-05-14
• Study First Posted: 2010-05-18
• Study Start: 2010-06-17
• Primary Completion: 2014-03-10
• Study Completion: 2018-12-31
• Status Verified: 2020-10
• Results First Submitted: 2020-10-16
• Results First Submitted QC: 2021-01-04
• Last Update Submitted: 2021-01-04
• Results First Posted: 2021-01-22
• Last Update Posted: 2021-01-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm I	bevacizumab	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.

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS) of Patients With Recurrent or Progressive Meningiomas Treated With Bevacizumab at 6 Months	From the start of treatment and up until 6 months of treatment or follow up	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).

Secondary Outcome Measures

Name	Time	Method
Safety Profile of Bevacizumab	Every 2 weeks or 3 weeks while on treatment up to 30 days after the last dose. The maximum duration any one patient was on treatment was approximately 5 years.	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
Number of Patients With Each Response	From start of treatment and approximately every 8 weeks for up to approximately 5 years ( maximum duration any one patient was on treatment)	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
Levels of VEGF, VEGRfR2 and HER2 Expression in Tumor Tissue as Compared to Response	At baseline and every 8 weeks until disease progression or death. The maximum duration any one patient was on treatment was approximately 5 years.	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.
Number of Patients Alive at 1 Year, 2 Years and 3 Years Post Treatment Initiation (Overall Survival) for Patients With Recurrent or Progressive Meningiomas Treated With Bevacizumab	At 1 year, 2 years, 3 years post treatment initiation	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.

Trial Locations

Locations (5)

Northwestern University; 🇺🇸 Chicago, Illinois, United States

Columbia University Medical Center; 🇺🇸 New York, New York, United States

Dana-Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

University of Virginia; 🇺🇸 Charlottesville, Virginia, United States

University of Washington; 🇺🇸 Seattle, Washington, United States