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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01767792
Recruitment Status : Active, not recruiting
First Posted : January 14, 2013
Results First Posted : May 27, 2020
Last Update Posted : August 5, 2020
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
Bruce Korf, MD, University of Alabama at Birmingham

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Neurofibromatosis Type 2
Progressive Vestibular Schwannomas
Intervention Drug: Bevacizumab
Enrollment 22
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Bevacizumab
Hide Arm/Group Description Safety and tolerability of bevacizumab for 2 years. Change in hearing response will also be monitored.
Period Title: Overall Study
Started 22
Completed 20
Not Completed 2
Arm/Group Title Bevacizumab
Hide Arm/Group Description

Follow participant for 2 years and assess hearing response rates

Bevacizumab: 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).

Overall Number of Baseline Participants 22
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 22 participants
29  (14.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants
Female
13
  59.1%
Male
9
  40.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants
Hispanic or Latino
2
   9.1%
Not Hispanic or Latino
18
  81.8%
Unknown or Not Reported
2
   9.1%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
2
   9.1%
White
20
  90.9%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Region of Enrollment   [1] 
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 22 participants
22
[1]
Measure Description: Participants enrolled in the United States
Word recognition score in target ear  
Median (Full Range)
Unit of measure:  Number correct words
Number Analyzed 22 participants
53
(6 to 82)
1.Primary Outcome
Title Improvement in Hearing
Hide Description Number of participants with a statistically significant increase in word recognition score on audiology compared to baseline.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
All participants treated with bevacizumab.
Arm/Group Title Bevacizumab
Hide Arm/Group Description:
Induction (high dose) therapy.
Overall Number of Participants Analyzed 22
Measure Type: Count of Participants
Unit of Measure: Participants
9
  40.9%
2.Secondary Outcome
Title Number of Participants With Adverse Events
Hide Description Number of participants with adverse events occurring in at least 10% of participants during induction therapy.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
All participants treated with bevacizumab.
Arm/Group Title Bevacizumab
Hide Arm/Group Description:
Induction (high dose) therapy.
Overall Number of Participants Analyzed 22
Measure Type: Count of Participants
Unit of Measure: Participants
22
 100.0%
3.Secondary Outcome
Title Tolerability of Bevacizumab During Induction (High Dose) Therapy
Hide Description Number of participants who did not stop treatment due to side effects or by participant/provider choice during induction period.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
All participants treated with bevacizumab.
Arm/Group Title Bevacizumab
Hide Arm/Group Description:
Induction (high dose) therapy.
Overall Number of Participants Analyzed 22
Measure Type: Count of Participants
Unit of Measure: Participants
21
  95.5%
4.Secondary Outcome
Title Durability of Hearing Response During Maintenance (Low Dose) Therapy
Hide Description Number of participants with hearing improvement during induction therapy who maintained hearing improvement relative to baseline during maintenance therapy as measured by word recognition score.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population is restricted to participants who achieved hearing improvement during induction (high dose) therapy.
Arm/Group Title Bevacizumab
Hide Arm/Group Description:
Maintenance (low dose) therapy.
Overall Number of Participants Analyzed 7
Measure Type: Count of Participants
Unit of Measure: Participants
4
  57.1%
5.Secondary Outcome
Title Changes in Pure Tone Average (PTA) on Audiology Compared With Baseline, Measured in Decibels (dBHL).
Hide Description Increase in pure tone average represents worsening of hearing and decrease in pure tone average represents improvement of hearing. Range for for pure tone average (PTA) is 0-110 dBHL (decibels).
Time Frame Weeks 25, 49, 73, 98
Hide Outcome Measure Data
Hide Analysis Population Description
All participants treated during maintenance (low dose) therapy.
Arm/Group Title Bevacizumab
Hide Arm/Group Description:
Maintenance (low dose) therapy.
Overall Number of Participants Analyzed 20
Least Squares Mean (Standard Error)
Unit of Measure: decibels (dBHL)
Change from week 25 to week 49 -1.19  (1.91)
Change from week 25 to week 73 1.05  (1.91)
Change from week 25 to week 98 -0.95  (2.09)
6.Secondary Outcome
Title Changes in Distress Related to Tinnitus During Induction (High Dose) Treatment.
Hide Description Self-reported distress measured using the tinnitus reaction questionnaire (TRQ). TRQ has 26 questions measured on a 5-point Likert scale from 0 (not at all) to 4 (almost all of the time). The total score is the sum of the responses with higher scores indicating more reported distress.
Time Frame 6 months (induction phase)
Hide Outcome Measure Data
Hide Analysis Population Description
Number of participants with data at baseline and month 6.
Arm/Group Title Bevacizumab
Hide Arm/Group Description:
Induction (high dose) therapy.
Overall Number of Participants Analyzed 21
Mean (Standard Deviation)
Unit of Measure: units on a scale
14.3  (18.2)
7.Secondary Outcome
Title Durability of Radiographic Response
Hide Description Count of participants who achieved a 20% or more reduction in tumor volume over baseline during induction (high dose) therapy and maintained this decrease during maintenance (low dose) therapy (decline in tumor volume from baseline of 20% or more).
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population is restricted to participants who achieved hearing improvement during induction (high dose) therapy.
Arm/Group Title Bevacizumab
Hide Arm/Group Description:
Maintenance (low dose) therapy.
Overall Number of Participants Analyzed 7
Measure Type: Count of Participants
Unit of Measure: Participants
5
  71.4%
Time Frame Adverse event data collected for 2 years
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Bevacizumab
Hide Arm/Group Description Safety and tolerability of bevacizumab for 2 years. Change in hearing response will also be monitored.
All-Cause Mortality
Bevacizumab
Affected / at Risk (%)
Total   0/22 (0.00%)    
Hide Serious Adverse Events
Bevacizumab
Affected / at Risk (%) # Events
Total   1/22 (4.55%)    
Nervous system disorders   
Headache  1  1/22 (4.55%)  1
1
Term from vocabulary, CTCAE 4.3
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Bevacizumab
Affected / at Risk (%) # Events
Total   22/22 (100.00%)    
Gastrointestinal disorders   
Diarrhea  1  4/22 (18.18%)  6
Nausea  1  4/22 (18.18%)  5
Abdominal pain  1  3/22 (13.64%)  3
Mucositis oral  1  3/22 (13.64%)  11
Investigations   
AST increased  1  3/22 (13.64%)  3
Metabolism and nutrition disorders   
Hyperglycemia  1  3/22 (13.64%)  3
Musculoskeletal and connective tissue disorders   
Arthralgia  1  3/22 (13.64%)  4
Back pain  1  3/22 (13.64%)  3
Nervous system disorders   
Fatigue  1  8/22 (36.36%)  17
Headache  1  7/22 (31.82%)  13
Renal and urinary disorders   
Proteinuria  1  4/22 (18.18%)  5
Reproductive system and breast disorders   
Irregular menstruation  1  6/22 (27.27%)  9
Respiratory, thoracic and mediastinal disorders   
Epistaxis  1  5/22 (22.73%)  8
Vascular disorders   
Hypertension  1  11/22 (50.00%)  28
1
Term from vocabulary, CTCAE 4.3
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Bruce Korf, MD, PhD
Organization: The University of Alabama at Birmingham
Phone: 205.934.4010
EMail: bkorf@uabmc.edu
Layout table for additonal information
Responsible Party: Bruce Korf, MD, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT01767792    
Other Study ID Numbers: AVF4807
W81XWH-12-1-0155 ( Other Grant/Funding Number: Dept. of Defense - US Army )
First Submitted: January 7, 2013
First Posted: January 14, 2013
Results First Submitted: April 15, 2020
Results First Posted: May 27, 2020
Last Update Posted: August 5, 2020