Phase 2 Study of Bevacizumab in Children and Young Adults With NF 2 and Progressive Vestibular Schwannomas
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|ClinicalTrials.gov Identifier: NCT01767792|
Recruitment Status : Completed
First Posted : January 14, 2013
Results First Posted : May 27, 2020
Last Update Posted : February 12, 2021
|Condition or disease||Intervention/treatment||Phase|
|Neurofibromatosis Type 2 Progressive Vestibular Schwannomas||Drug: Bevacizumab||Phase 2|
Subjects will be treated with open-label bevacizumab 10 mg/kg every 2 weeks for 24 weeks (induction therapy). Clinical response will be assessed by audiology and MRI at weeks 12 and 24. Subjects with hearing decline at weeks 12 or 24 will be taken off of protocol. At 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).
Subjects will be allowed to increase their bevacizumab dose to 10 mg/kg every 2 weeks during maintenance therapy if they experience hearing decline during maintenance therapy (defined as decrease in word recognition score below the 95% critical difference compared with the word recognition score at baseline, Appendix A). Subjects will be taken off of study if their word recognition score does not remain within the 95% critical difference after receiving bevacizumab 10 mg/kg every 2 weeks.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||22 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Open-label, Phase 2 Study of Bevacizumab in Children and Young Adults With Neurofibromatosis 2 and Progressive Vestibular Schwannomas That Are Poor Candidates for Standard Treatment With Surgery or Radiation|
|Actual Study Start Date :||May 15, 2013|
|Actual Primary Completion Date :||January 1, 2019|
|Actual Study Completion Date :||February 1, 2020|
Follow participant for 2 years and assess hearing response rates
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).
- Improvement in Hearing [ Time Frame: 6 months ]Number of participants with a statistically significant increase in word recognition score on audiology compared to baseline.
- Number of Participants With Adverse Events [ Time Frame: 6 months ]Number of participants with adverse events occurring in at least 10% of participants during induction therapy.
- Tolerability of Bevacizumab During Induction (High Dose) Therapy [ Time Frame: 6 months ]Number of participants who did not stop treatment due to side effects or by participant/provider choice during induction period.
- Durability of Hearing Response During Maintenance (Low Dose) Therapy [ Time Frame: 2 years ]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.
- Changes in Pure Tone Average (PTA) on Audiology Compared With Baseline, Measured in Decibels (dBHL). [ Time Frame: Weeks 25, 49, 73, 98 ]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).
- Changes in Distress Related to Tinnitus During Induction (High Dose) Treatment. [ Time Frame: 6 months (induction phase) ]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.
- Durability of Radiographic Response [ Time Frame: 2 years ]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).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01767792
|United States, California|
|Children's Hospital Los Angeles|
|Los Angeles, California, United States, 90027|
|United States, District of Columbia|
|Children's National Medical Center|
|Washington, District of Columbia, United States, 20010|
|United States, Georgia|
|Children's HealthCare of Atlanta|
|Atlanta, Georgia, United States, 30324|
|United States, Illinois|
|University of Chicago|
|Chicago, Illinois, United States, 60637|
|United States, Indiana|
|Indianapolis, Indiana, United States, 46202|
|United States, Maryland|
|National Cancer Institute (NCI)|
|Bethesda, Maryland, United States, 20892|
|United States, Massachusetts|
|Children' Hospital Boston and Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02115|
|United States, Missouri|
|Washington University - St. Louis|
|Saint Louis, Missouri, United States, 63110|
|United States, New York|
|New York University Medical Center|
|New York, New York, United States, 10016|
|United States, Ohio|
|Cincinnati Children's Hospital Medical Center|
|Cincinnati, Ohio, United States, 45229-4006|
|United States, Pennsylvania|
|Children's Hospital of Philadelphia|
|Philadelphia, Pennsylvania, United States, 19096|
|United States, Utah|
|University of Utah|
|Salt Lake City, Utah, United States, 84132|
|Study Chair:||Scott Plotkin, MD||Massachusetts General Hospital|