Bevacizumab in Treating Patients With Recurrent or Progressive Meningiomas

NCT01125046 | Completed Phase 2 Results DMC

• 3 other identifiers: NU 09C2NCI-2010-00843STU00024715
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 5

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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)

• 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.

• 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.

• 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

Study Arms (1)

Arm I

EXPERIMENTAL

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

Interventions

bevacizumab BIOLOGICAL

Given IV

Also known as: anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, anti-VEGF rhuMAb, Avastin, recombinant humanized anti-VEGF monoclonal antibody, rhuMAb VEGF

Arm I

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Northwestern University: lead

Study Sites (5)

Northwestern University

Chicago, Illinois, 60611, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

University of Virginia

Charlottesville, Virginia, 22903, United States

Location

University of Washington

Seattle, Washington, 98109-1023, United States

Location

MeSH Terms

Conditions

Neuroma, Acoustic; Meningioma; Ependymoma; Neurofibromatosis 1; Neurofibromatosis 2; Brain Neoplasms

Interventions

Bevacizumab

Condition Hierarchy (Ancestors)

Neurilemmoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neuroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Cranial Nerve Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Peripheral Nervous System Neoplasms; Vestibulocochlear Nerve Diseases; Retrocochlear Diseases; Ear Diseases; Otorhinolaryngologic Diseases; Otorhinolaryngologic Neoplasms; Cranial Nerve Diseases; Nervous System Diseases; Neoplasms, Vascular Tissue; Meningeal Neoplasms; Central Nervous System Neoplasms; Glioma; Neoplasms, Neuroepithelial; Neoplasms, Glandular and Epithelial; Neurofibromatoses; Neurofibroma; Neoplastic Syndromes, Hereditary; Neurocutaneous Syndromes; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Brain Diseases; Central Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Priya Kumthekar, MD
• Organization: Northwestern University

Priya.Kumthekar@nm.org

Study Officials

• Priya Kumthekar, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2010
• First Posted: May 18, 2010
• Study Start: June 17, 2010
• Primary Completion: March 10, 2014
• Study Completion: December 31, 2018
• Last Updated: January 22, 2021
• Results First Posted: January 22, 2021

Record last verified: 2020-10

Locations

US (5)