Phase 2 Study of Bevacizumab in Children and Young Adults With NF 2 and Progressive Vestibular Schwannomas

NCT01767792 | Completed Phase 2 Results DMC

• 2 other identifiers: AVF4807W81XWH-12-1-0155
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 12

Brief Summary

To determine the hearing response rate at 24 weeks after treatment with bevacizumab for symptomatic vestibular schwannomas (VS) in children and young adults with Neurofibromatosis Type 2 (NF 2).

Conditions

Neurofibromatosis Type 2; Progressive Vestibular Schwannomas

Keywords

Neurofibromatosis Type 2; Progressive Vestibular Schwannomas

Outcome Measures

Primary Outcomes (1)

• Improvement in Hearing

  Number of participants with a statistically significant increase in word recognition score on audiology compared to baseline.

  6 months

Secondary Outcomes (6)

• Number of Participants With Adverse Events

  6 months

• Tolerability of Bevacizumab During Induction (High Dose) Therapy

  6 months

• Durability of Hearing Response During Maintenance (Low Dose) Therapy

  2 years

• Changes in Pure Tone Average (PTA) on Audiology Compared With Baseline, Measured in Decibels (dBHL).

  Weeks 25, 49, 73, 98

• Changes in Distress Related to Tinnitus During Induction (High Dose) Treatment.

  6 months (induction phase)

Study Arms (1)

Bevacizumab

EXPERIMENTAL

Follow participant for 2 years and assess hearing response rates

Drug: Bevacizumab

Interventions

Bevacizumab DRUG

Treatment will be administered on an outpatient basis. Bevacizumab is administered by IV infusion at a dose of 10 mg/kg every 2 weeks for 24 weeks (induction therapy, see Schema). One cycle lasts 28 days and includes two infusions of bevacizumab. Clinical response will be assessed by audiology and MRI at weeks 12 and 24. Subjects with hearing decline at weeks 12 and 24 will be taken off of protocol. After week 24, patients with a clinical response or stable disease (together comprising "clinical benefit") will transition to maintenance therapy with bevacizumab. During the maintenance phase, subjects will be treated with open-label bevacizumab 5 mg/kg every 3 weeks for up to 72 weeks. Subjects will be followed with audiology and MRI scans every 12 weeks. The total time of the study will be 96 weeks (24 weeks induction + 72 weeks maintenance).

Also known as: rhuMAb, Vascular Endothelial Growth Factor (VEGF), Avastin®

Bevacizumab

Eligibility Criteria

• Age: 6 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 Neurofibromatosis 2 (NF2) gene.
• Patients must have measurable disease, defined as at least one VS \> 1.0 ml (on volumetric analysis) that can be accurately measured by contrast-enhanced cranial MRI scan with fine cuts through the internal auditory canal (3 mm slices, no skip).
• Age 6 years or greater (no upper limit) on day 1 of treatment. Given the potential risk of long-term bevacizumab use, children under age 6 are not eligible for treatment. No upper limit for adults.
• Life expectancy of greater than 1 year.
• Karnofsky performance status ≥ 70.
• Participants must have normal organ and marrow function as defined below with definitions micro liter (mcL), Aspartate aminotransferase (AST), Serum glutamic oxaloacetic transaminase (SGOT), Alanine aminotransferase (ALT), Serum glutamic pyruvic transaminase (SGPT):
• Leukocytes \> 3,000/mcL
• Absolute neutrophil count \> 1,500/mcL
• Platelets \> 100,000/mcL
• Total bilirubin within normal institutional limits
• AST (SGOT)/ALT (SGPT) \< 2.5 X institutional upper limit of normal
• Patients must have a creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥60ml/min/1.73 m2 or a normal serum creatinine based on age described in the table below:
• Age Maximum Serum Creatinine (mg/dL) 6 to \< 10 years 1(Male) 1(Female) 10 to \< 13 years 1.2(Male) 1.2(Female) 13 to \< 16 years 1.5(Male) 1.4(Female
• ≥ 16 years 1.7(Male) 1.4(Female)
• Subjects must have a target VS with the following qualities:

You may not qualify if:

• Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study.
• Patients who have had chemotherapy 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. Prior radiation treatment to the target vestibular schwannoma is allowed if provided 3 years prior to participation in the clinical trial. Prior radiation treatment to non-target tumors is allowed.
• Participants may not be receiving any other study agents.
• Patients with nervous system tumors associated with NF2 (e.g., schwannomas, meningiomas, ependymomas, or gliomas) will not be excluded from this clinical trial unless (in the opinion of the investigator) these tumors are growing and are likely to require treatment during the clinical trial.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to bevacizumab.
• 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.
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements.
• History of arterial/myocardial disease.
• Clinically significant cardiovascular disease, such as:
• Inadequately controlled hypertension (HTN) (for adults: Systolic Blood Pressure (SBP) \> 160 mmHg and/or Diastolic Blood Pressure (DBP) \> 90 mmHg despite antihypertensive medication; for children: please refer to Appendix D for age-appropriate values indicating ≥ Grade 2)
• History of cerebrovascular accident (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

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• Genentech, Inc.: collaborator

Study Sites (12)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Children's HealthCare of Atlanta

Atlanta, Georgia, 30324, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Indiana Unversity

Indianapolis, Indiana, 46202, United States

Location

National Cancer Institute (NCI)

Bethesda, Maryland, 20892, United States

Location

Children' Hospital Boston and Massachusetts General Hospital

Boston, Massachusetts, 02115, United States

Location

Washington University - St. Louis

St Louis, Missouri, 63110, United States

Location

New York University Medical Center

New York, New York, 10016, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229-4006, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19096, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

MeSH Terms

Conditions

Neurofibromatosis 2

Interventions

Bevacizumab; Vascular Endothelial Growth Factor A

Condition Hierarchy (Ancestors)

Neuroma, Acoustic; Neurilemmoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neurofibromatoses; Neurofibroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Neuroma; Neoplastic Syndromes, Hereditary; Vestibulocochlear Nerve Diseases; Retrocochlear Diseases; Ear Diseases; Otorhinolaryngologic Diseases; Otorhinolaryngologic Neoplasms; Cranial Nerve Neoplasms; Cranial Nerve Diseases; Nervous System Diseases; 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; Vascular Endothelial Growth Factors; Angiogenic Proteins; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors

Results Point of Contact

• Title: Bruce Korf, MD, PhD
• Organization: The University of Alabama at Birmingham

bkorf@uabmc.edu

205.934.4010

Study Officials

• Scott Plotkin, MD

  Massachusetts General Hospital

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 7, 2013
• First Posted: January 14, 2013
• Study Start: May 15, 2013
• Primary Completion: January 1, 2019
• Study Completion: February 1, 2020
• Last Updated: February 12, 2021
• Results First Posted: May 27, 2020

Record last verified: 2021-01

Locations

US (12)