Bevacizumab for Symptomatic Vestibular Schwannoma in Neurofibromatosis Type 2 (NF2)

NCT01207687 | Completed Phase 2 Results

• 5 other identifiers: NCI-2012-02987J1002NA_000347328248P30CA006973
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 3

Brief Summary

People who have neurofibromatosis type 2 (NF2) can have tumors that grow on the auditory nerves and cause hearing loss. These tumors are called vestibular schwannomas (VSs), or acoustic neuromas. People with NF2 can also get schwannomas in other parts of their body, as well as tumors called meningiomas and ependymomas. Because VSs can cause hearing loss, many people with NF2 will have treatment to preserve their hearing. This treatment usually involves surgery. Because surgery has risks and is not able to help everyone with VSs, other methods of treatment are being explored. One area of exploration is looking to see if there is a drug that can be taken that might prevent the VSs from growing larger and causing hearing loss or brainstem compression. This study is exploring whether a drug that is approved by the FDA and is currently used to treat other tumors might also work to treat VSs. Based on people who have taken this drug to treat VSs already, there is some reason to think that it might be helpful to certain people with NF2. People enrolled in this study will receive the drug one time every three weeks for one year by infusion. This study will follow subjects over the course of the year that the person is taking the drug and for six months after the drug is stopped. This study is recruiting people who have NF2 and are currently having symptoms of tinnitus, dizziness, and/or hearing loss from their VSs. If you have NF2 and are currently having symptoms caused by your VSs, you may be eligible to participate.

Conditions

Vestibular Schwannoma; Neurofibromatosis Type 2

Outcome Measures

Primary Outcomes (1)

• Proportion of Patients With Hearing Response

  A hearing response was defined as increased word recognition score above the 95% critical threshold that is maintained across two sequential evaluation time points. The word recognition score (WRS) is the percentage of phonetically-balanced, monosyllabic words that a patient can accurately repeat presented at either most comfortable level or most intelligible level.The proportion of patients with hearing response in the target ear was estimated using a binomial distribution along with 95% confidence intervals.

  Baseline to 12 months

Secondary Outcomes (21)

• Incidence of Serious or Life Threatening Toxicities

  Up to 6 months post-treatment

• Radiographic Response

  Baseline to 6 months post-treatment

• Median Percent Change in Target Vestibular Schwannoma Volume Using Volumetric MRI

  Baseline to 12 months

• Number of Participants With Changes in Function of the Auditory System

  Baseline to 6 months post-treatment

• Percent Change in Median Vascular Permeability (Ktrans)

  Baseline to week 72

Study Arms (1)

Treatment (bevacizumab)

EXPERIMENTAL

Patients receive bevacizumab IV over 30-90 minutes once every 3 weeks. Courses repeat every 6 weeks for up to 48 weeks in the absence of disease progression or unacceptable toxicity.

Biological: bevacizumab; Other: laboratory biomarker analysis; Procedure: quality-of-life assessment

Interventions

bevacizumab BIOLOGICAL

Given IV

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

Treatment (bevacizumab)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (bevacizumab)

quality-of-life assessment PROCEDURE

Ancillary studies

Also known as: quality of life assessment

Treatment (bevacizumab)

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have a confirmed diagnosis of neurofibromatosis 2 by fulfilling National Institute of Health (NIH) criteria or Manchester criteria, or by detection of a causative mutation in the NF2 gene
• The NIH criteria (82) includes presence of:
• Bilateral vestibular schwannomas, OR
• First-degree relative with NF2 and EITHER unilateral eighth nerve mass OR two of the following: neurofibroma, meningioma, glioma, schwannoma, juvenile posterior subcapsular lenticular opacity
• The Manchester criteria (101) includes presence of:
• Bilateral vestibular schwannomas, OR
• First-degree relative with NF2 and EITHER unilateral eighth nerve mass OR two of the following: neurofibroma, meningioma, glioma, schwannoma, juvenile posterior subcapsular lenticular opacity, OR
• Unilateral vestibular schwannoma AND any two of: neurofibroma, meningioma, glioma, schwannoma, juvenile posterior subcapsular lenticular opacity, OR
• Multiple meningiomas (two or more) AND unilateral vestibular schwannoma OR any two of: schwannoma, glioma, neurofibroma, cataract
• Patients must have measurable disease, defined as at least one VS \>= 1.5 cm (on longest diameter) as measured by contrast-enhanced cranial MRI scan with fine cuts through the internal auditory canal (3 mm slices, no skip)
• Life expectancy of greater than 6 months
• ECOG performance status (Karnofsky \>= 60% or Lansky Score \>= 60)
• Patients must have normal organ and marrow function as defined below:
• Leukocytes \>= 3,000/mcL
• Absolute neutrophil count \>= 1,500/mcL

You may not qualify if:

• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• Patients may not be receiving any other investigational agents
• Patients with nervous system tumors associated with NF2 (e.g., schwannomas, meningiomas, ependymomas, or gliomas) will not be excluded from this clinical trial as long as these tumors do not require treatment with radiation, surgery, or medical treatment at the time of enrollment on trial
• Patients with known hypersensitivity of Chinese hamster ovary cell products, other recombinant human antibodies, or compounds of similar chemical or biologic composition to bevacizumab
• Inability to tolerate periodic MRI scans or gadolinium contrast without general anesthesia
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements
• Clinically significant cardiovascular disease, such as:
• Inadequately controlled HTN (adult subjects: SBP \> 160 mmHg and/or DBP \> 90 mmHg despite antihypertensive medication, pediatric subjects: Requirement for antihypertensive treatment prior to enrollment, or diastolic blood pressure \> 95th percentile for age)
• History of CVA within 12 months
• Myocardial infarction or unstable angina within 12 months
• New York heart association grade II or greater congestive heart failure
• Serious and inadequately controlled cardiac arrhythmia
• Significant vascular disease (e.g. aortic aneurysm, history of aortic dissection)
• Clinically significant peripheral vascular disease
• Pregnant women (positive pregnancy test) are excluded from this study because bevacizumab is an anti-angiogenic agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with bevacizumab, breastfeeding should be discontinued if the mother is treated with bevacizumab; both fertile men and women must agree to use adequate contraceptive measures during study therapy and for at least 6 months after the completion of bevacizumab therapy; abstinence is considered an adequate contraceptive measure

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (3)

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

National Cancer Institute

Rockville, Maryland, 20850, United States

Location

Massachusetts General Hospital

Charlestown, Massachusetts, 02129, United States

Location

Related Publications (1)

• Blakeley JO, Ye X, Duda DG, Halpin CF, Bergner AL, Muzikansky A, Merker VL, Gerstner ER, Fayad LM, Ahlawat S, Jacobs MA, Jain RK, Zalewski C, Dombi E, Widemann BC, Plotkin SR. Efficacy and Biomarker Study of Bevacizumab for Hearing Loss Resulting From Neurofibromatosis Type 2-Associated Vestibular Schwannomas. J Clin Oncol. 2016 May 10;34(14):1669-75. doi: 10.1200/JCO.2015.64.3817. Epub 2016 Mar 14.

  PMID: 26976425 RESULT

MeSH Terms

Conditions

Neuroma, Acoustic; Neurofibromatosis 2

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; Neurofibromatoses; Neurofibroma; Neoplastic Syndromes, Hereditary; Neurocutaneous Syndromes; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

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: Dr. Jaishri Blakeley
• Organization: Johns Hopkins Comprehensive Neurofibromatosis Center

jblakel3@jhmi.edu

410-614-3853

Study Officials

• Jaishri Blakeley

  Johns Hopkins University/Sidney Kimmel Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: September 1, 2010
• First Posted: September 23, 2010
• Study Start: October 1, 2010
• Primary Completion: February 1, 2013
• Study Completion: March 1, 2014
• Last Updated: August 27, 2018
• Results First Posted: August 17, 2017

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)