Bevacizumab in Treating Patients With Recurrent or Progressive Meningiomas

Neurofibromatosis Type 1 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01125046
• Other study ID #: NU 09C2
• Secondary ID: NCI-2010-00843ST
• Status: Completed
• Phase: Phase 2
• Start date: June 17, 2010
• Est. completion date: December 31, 2018

Study information

• Verified date: October 2020
• Source: Northwestern University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: December 31, 2018
• Est. primary completion date: March 10, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acoustic Schwannoma
• Adult Anaplastic Meningioma
• Adult Ependymoma
• Adult Grade I Meningioma
• Adult Grade II Meningioma
• Adult Meningeal Hemangiopericytoma
• Adult Papillary Meningioma
• Ependymoma
• Hemangiopericytoma
• Meningioma
• Neurilemmoma
• Neurofibroma
• Neurofibromatoses
• Neurofibromatosis 1
• Neurofibromatosis 2
• Neurofibromatosis Type 1
• Neurofibromatosis Type 2
• Neuroma, Acoustic
• Recurrent Adult Brain Tumor

Intervention

Biological:
• bevacizumab
Given IV

Locations

Country	Name	City	State
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	University of Virginia	Charlottesville	Virginia
United States	Northwestern University	Chicago	Illinois
United States	Columbia University Medical Center	New York	New York
United States	University of Washington	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Northwestern University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS) of Patients With Recurrent or Progressive Meningiomas Treated With Bevacizumab at 6 Months	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).	From the start of treatment and up until 6 months of treatment or follow up
Secondary	Number of Patients With Each Response	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	From start of treatment and approximately every 8 weeks for up to approximately 5 years ( maximum duration any one patient was on treatment)
Secondary	Safety Profile of Bevacizumab	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	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.
Secondary	Levels of VEGF, VEGRfR2 and HER2 Expression in Tumor Tissue as Compared to Response	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.	At baseline and every 8 weeks until disease progression or death. The maximum duration any one patient was on treatment was approximately 5 years.
Secondary	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	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.	At 1 year, 2 years, 3 years post treatment initiation