Neurofibromatosis Type 2Phase 2NCT01767792
Phase 2 Study of Bevacizumab in Children and Young Adults With NF 2 and Progressive Vestibular Schwannomas
A Phase 2 study testing Bevacizumab in people with Neurofibromatosis Type 2 and Progressive Vestibular Schwannomas, run by University of Alabama at Birmingham at 12 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 6 years and older
- Conditions the study is for
- Neurofibromatosis Type 2, Progressive Vestibular Schwannomas
- What is being tested?
- Bevacizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 12 sitesUnited States
- Study dates
- 15 May 2013to 1 Feb 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- 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.
Show all 30Show fewer
- 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
- Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection)
- Clinically significant peripheral vascular disease
- Pregnant women 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 of adverse events in nursing infants secondary to treatment of the mother with bevacizumab, breastfeeding should be discontinued if the mother is treated with bevacizumab. These potential risks may also apply to other agents used in this study.
- HIV-positive patients or cancer survivors are eligible for this study if they fulfill all other eligibility criteria.
- Concurrent use of anti-coagulant drugs (not including prophylactic doses), history of coagulopathy, or evidence of bleeding diathesis or coagulopathy.
- Imaging (CT or MRI) evidence of hemorrhage deemed significant by the treating physician (> grade 1). Subjects with history of central nervous system (CNS) hemorrhage are not eligible.
- Urine protein should be screened by urine analysis for Urine Protein Creatinine (UPC) ratio. For UPC ratio > 0.5, 24-hour urine protein should be obtained and the level should be <1000 mg for patient enrollment.
- Serious or non-healing wound, ulcer or bone fracture.
- History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to day 1.
- Invasive procedures defined as follows:
- Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to Day 1 therapy
- Brain biopsy within 28 days prior to day 1 of therapy (wounds must be fully healed from brain biopsies performed more than 28 days prior to day 1 of therapy)
- Anticipation of need for major surgical procedures during the course of the study
- Core biopsy within 7 days prior to D1 therapy
- Prior treatment with bevacizumab.
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
United States12 sites
Children's HealthCare of Atlanta
Atlanta, Georgia, 30324
National Cancer Institute (NCI)
Bethesda, Maryland, 20892
Children' Hospital Boston and Massachusetts General Hospital
Boston, Massachusetts, 02115
University of Chicago
Chicago, Illinois, 60637
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229-4006
Indiana Unversity
Indianapolis, Indiana, 46202
Children's Hospital Los Angeles
Los Angeles, California, 90027
New York University Medical Center
New York, New York, 10016
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19096
University of Utah
Salt Lake City, Utah, 84132
Washington University - St. Louis
St Louis, Missouri, 63110
Children's National Medical Center
Washington D.C., District of Columbia, 20010
About this study
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
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).
Read the detailed description
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.
- Being tested
- Bevacizumab
- Keywords
- Neurofibromatosis Type 2, Progressive Vestibular Schwannomas
- Medical subject headings
- Neurofibromatosis 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BevacizumabDrug
Also called rhuMAb, Vascular Endothelial Growth Factor (VEGF), Avastin®
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).
| Study group | Role | What they receive |
|---|---|---|
| Bevacizumab | Experimental | Follow participant for 2 years and assess hearing response rates Receives: Drug: Bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Improvement in Hearing
Number of participants with a statistically significant increase in word recognition score on audiology compared to baseline.
Measured: 6 months
Secondary outcomes (6)
Number of Participants With Adverse Events
Number of participants with adverse events occurring in at least 10% of participants during induction therapy.
Measured: 6 months
Tolerability of Bevacizumab During Induction (High Dose) Therapy
Number of participants who did not stop treatment due to side effects or by participant/provider choice during induction period.
Measured: 6 months
Durability of Hearing Response During Maintenance (Low Dose) Therapy
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.
Measured: 2 years
Changes in Pure Tone Average (PTA) on Audiology Compared With Baseline, Measured in Decibels (dBHL).
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).
Measured: Weeks 25, 49, 73, 98
Changes in Distress Related to Tinnitus During Induction (High Dose) Treatment.
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.
Measured: 6 months (induction phase)
Durability of Radiographic Response
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).
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2013 (estimated)
- Study start15 May 2013
- Primary completion1 Jan 2019
- Study completion1 Feb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Neurofibromatosis Type 2Studies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Principal investigator, Bruce Korf, MD, University of Alabama at Birmingham
- Investigators
- Scott Plotkin, MD, Study chair, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01767792
- Sponsor's protocol ID
- AVF4807
- Other IDs
- W81XWH-12-1-0155
- Status last verified
- Jan 2021
- First submitted
- 7 Jan 2013
- Last updated
- 12 Feb 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01767792
- Acronym / sponsor ID
- AVF4807
- Keywords
- Neurofibromatosis Type 2, Progressive Vestibular Schwannomas
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- 15 May 2013 (actual)
- Primary completion
- 1 Jan 2019 (actual)
- Study completion
- 1 Feb 2020 (actual)
- First posted
- 14 Jan 2013 (estimated)
- Results
- Posted 27 May 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bevacizumab | Experimental | Drug: BevacizumabFollow participant for 2 years and assess hearing response rates |
Who may qualify
- Ages
- 6 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (30 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BevacizumabAlso: rhuMAb, Vascular Endothelial Growth Factor (VEGF), Avastin®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). | Drug | Bevacizumab |
Primary outcome
Improvement in Hearing
Time frame: 6 months
Number of participants with a statistically significant increase in word recognition score on audiology compared to baseline.
6 secondary outcomes
Number of Participants With Adverse Events
Time frame: 6 months
Tolerability of Bevacizumab During Induction (High Dose) Therapy
Time frame: 6 months
Durability of Hearing Response During Maintenance (Low Dose) Therapy
Time frame: 2 years
Changes in Pure Tone Average (PTA) on Audiology Compared With Baseline, Measured in Decibels (dBHL).
Time frame: Weeks 25, 49, 73, 98
Changes in Distress Related to Tinnitus During Induction (High Dose) Treatment.
Time frame: 6 months (induction phase)
Durability of Radiographic Response
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Scott Plotkin, MD study chair
Massachusetts General Hospital
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bevacizumab in people with Neurofibromatosis Type 2 and Progressive Vestibular Schwannomas, run by University of Alabama at Birmingham at 12 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 May 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Improvement in Hearing (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Feb 2021.