Neurofibromatosis 2Phase 2NF110NCT04283669
Phase 2 Clinical Trial of Crizotinib for Children and Adults With Neurofibromatosis Type 2 and Progressive Vestibular Schwannomas
A Phase 2 study testing Crizotinib in people with Neurofibromatosis 2 and Progressive Vestibular Schwannoma (VS), run by University of Alabama at Birmingham at 15 sites in United States.
Trial summary
Subjects with Neurofibromatosis Type 2 (NF2) and progressive vestibular schwannoma (VS) will be treated with crizotinib administered orally. Crizotinib will be taken continuously until disease progression or unacceptable toxicity, in continuous treatment cycles of 28 days each, for a maximum of 12 cycles. Read more about this study
- Who is it for?
- Ages 6 years and older
- Conditions the study is for
- Neurofibromatosis 2, Progressive Vestibular Schwannoma (VS)
- What is being tested?
- Crizotinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 15 sitesUnited States
- Study dates
- 18 Feb 2020to 25 Feb 2025
- 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
- Participants must meet the following criteria on screening examination to be eligible to participate in the study:
- 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 include 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.
Show all 31Show fewer
- The Manchester criteria include 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 progressive and measurable disease, defined as at least one VS with the following qualities:
- ≥ 0.75 ml (on volumetric analysis) that can be accurately measured by contrast-enhanced cranial MRI scan with fine cuts through the internal auditory canal (1 mm slices, no skip)
- MRI evidence of progression over the past 18 months (defined as ≥20% annualized increase in volume)
- Age ≥ 6 years on day 1 of treatment.
- Life expectancy of greater than 1 year.
- Lansky/Karnofsky performance status ≥ 60
- Organ and marrow function as defined below:
- Absolute neutrophil count ≥ 1,500/ μl
- Platelets ≥ 100,000/ μl
- Total bilirubin within ≤ 1.5 X institutional upper limit of normal
- AST (SGOT)/ALT (SGPT) ≤ 2.5 X institutional upper limit of normal
- Patients must have a creatinine clearance or radioisotope GFR ≥60ml/min/1.73 ≥60ml/min/1.73 m2 or a normal serum creatinine based on age/gender described in the table below:
- Age: 6 to < 10 years with a Maximum Serum Creatinine (mg/dL) of 1 for Male and 1 for Female
- Age: 10 to < 13 years with a Maximum Serum Creatinine (mg/dL) of 1.2 for Male and 1.2 for Female
- Age: 13 to < 16 years with a Maximum Serum Creatinine (mg/dL) of 1.5 for Male and 1.4 for Female
- Age: ≥ 16 years with a Maximum Serum Creatinine (mg/dL) of 1.7 for Male and 1.4 for Female
- The threshold creatinine values in this Table were derived from the Schwartz formula for estimating GFR utilizing child length and stature data published by the CDC.
- Fully recovered from acute toxic effects of any prior chemotherapy, biological modifiers or radiotherapy
- Any neurologic deficits must be stable for ≥1 week
- Patient or parent/legal guardian must be able to provide signed informed consent and assent (as applicable for minors)
Who cannot join
- Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study.
- Patients currently receiving medical anticancer therapies or who have received medical anticancer therapies within 4 weeks of the start of study drug (including chemotherapy and molecular targeted agents), as these may interfere with the study drug
- Monoclonal antibody treatment and/or agents with prolonged half-lives: At least three half-lives must have elapsed from the last dose prior to enrollment
- Radiation therapy to a study target tumor within 1 year prior to enrollment, or any radiation therapy within 4 weeks prior to enrollment, as these may interfere with our ability to assess response to study drug
- Prior treatment with any investigational drug within the preceding 4 weeks, as they may interfere with the study drug
- Unstable or rapidly progressive disease, including patients who require glucocorticoids for symptomatic control of brain or spinal tumors, as this would represent a high risk for inability to comply with the study requirements
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- Use of drugs or foods that are known potent CYP3A4 inhibitors, including but not limited to ketoconazole, itraconazole, miconazole, clarithromycin, erythromycin, ritonavir, indinavir, nelfinavir, saquinavir, amprenavir, delavirdine, nefazodone, diltiazem, verapamil, and grapefruit juice, as this would interfere with study drug metabolism
- Use of drugs that are known potent CYP3A4 inducers, including but not limited to carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, tipranavir, ritonavir, and St. John's wort, as this would interfere with study drug metabolism
- Use of drugs that are CYP3A4 substrates with narrow therapeutic indices, including but not limited to pimozide, aripiprazole, triazolam, dihydroergotamine, ergotamine, astemizole, cisapride, terfenadine and halofantrine, as this would interfere with study drug metabolism
- Ongoing cardiac dysrhythmias of CTCAE grade ≥2, uncontrolled atrial fibrillation of any grade or prolonged QTc interval (>480 msec), as patients with these conditions would be expected to have an increased risk for cardiac toxicity related to study drug
- Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
- symptomatic congestive heart failure of New York heart Association Class III or IV
- unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease
- severely impaired lung function as defined as spirometry and DLCO that is 50% of the normal predicted value and/or O2 saturation that is 90% or less at rest on room air
- active (acute or chronic) or uncontrolled severe infections liver disease, such as cirrhosis or severe hepatic impairment (Child-Pugh class C)
- Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of crizotinib (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
- Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. Adequate contraception must be used throughout the trial and for 90 days after the last dose of study drug, as the effects of crizotinib on an unborn fetus are not known. Females of childbearing potential must have a negative serum pregnancy test within 7 days prior to administration of crizotinib.
- Male patients whose sexual partner(s) are women of child bearing potential, who are not willing to use adequate contraception during the study and for 90 days after the last dose of study drug.
- History of significant noncompliance to medical regimens that would jeopardize compliance with study therapy
- Patients unwilling to or unable to comply with the study protocol
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
United States15 sites
Children's HealthCare of Atlanta (Site 950)
Atlanta, Georgia, 30324
Johns Hopkins University (Site 250)
Baltimore, Maryland, 21287
The University of Alabama at Birmingham (Site 700)
Birmingham, Alabama, 35294
Children's Hospital Boston (Site 725)
Boston, Massachusetts, 02115
Lurie Childrens Hospital of Chicago (Site 350)
Chicago, Illinois, 60611
University of Chicago (Site 850)
Chicago, Illinois, 60637
Cincinnati Children's Hospital Medical Center (Site 800)
Cincinnati, Ohio, 45229-3039
Childrens Medical Center - Univ. of Texas SW (Site 917)
Dallas, Texas, 75235
Indiana University (Site 400)
Indianapolis, Indiana, 46202
Univ of California @ Los Angeles (Site 325)
Los Angeles, California, 90027
New York University Medical Center (Site 200)
New York, New York, 10016
Memorial Sloan Kettering Cancer Center (Site 210)
New York, New York, 10065
Children's Hospital of Philadelphia (Site 750)
Philadelphia, Pennsylvania, 19096
Washington University - St. Louis (Site 900)
St Louis, Missouri, 63110
Children's National Medical Center (Site 775)
Washington D.C., District of Columbia, 20010
About this study
Official title: Open-label, Phase 2 Clinical Trial of Crizotinib for Children and Adults With Neurofibromatosis Type 2 and Progressive Vestibular Schwannomas
Subjects with Neurofibromatosis Type 2 (NF2) and progressive vestibular schwannoma (VS) will be treated with crizotinib administered orally. Crizotinib will be taken continuously until disease progression or unacceptable toxicity, in continuous treatment cycles of 28 days each, for a maximum of 12 cycles.
Read the detailed description
Subjects with Neurofibromatosis Type 2 (NF2) and progressive vestibular schwannoma (VS) will be treated with crizotinib administered orally. Crizotinib will be taken continuously until disease progression or unacceptable toxicity, in continuous treatment cycles of 28 days each, for a maximum of 12 cycles. Clinical response will be assessed by MRI (volumetrics, primary objective) and audiology at the end of every 3rd cycle. Subjects with volumetric tumor progression will be taken off protocol. Patients who complete 12 cycles of treatment without disease progression, but within the following 24 weeks show subsequent disease progression (defined as >20% increase in target tumor volume compared to off-treatment volume), will be eligible for re-treatment on study for up to 48 additional weeks, provided they still meet study eligibility criteria.
- Being tested
- Crizotinib
- Medical subject headings
- Neurofibromatosis 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CrizotinibDrug
Oral
| Study group | Role | What they receive |
|---|---|---|
| Open Label Continuous Treatment | Other | Subjects with Neurofibromatosis Type 2 (NF2) and progressive vestibular schwannoma (VS) will be treated with crizotinib administered orally. Crizotinib will be taken continuously until disease progression or unacceptable toxicity, in continuous treatment cycles of 28 days each, for a maximum of 12 cycles. Clinical response will be assessed by MRI (volumetrics, primary objective) and audiology at the end of every 3rd cycle. Subjects with volumetric tumor progression will be taken off protocol. Patients who complete 12 cycles of treatment without disease progression, but within the following 24 weeks show subsequent disease progression (defined as >20% increase in target tumor volume compared to off-treatment volume), will be eligible for re-treatment on study for up to 48 additional weeks, provided they still meet study eligibility criteria. Receives: Drug: Crizotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Volumetric Response Rate
To evaluate efficacy, imaging response is treated as a binary variable whereby patients who achieve a volumetric response (greater than 20% reduction in tumor volume) in the target tumor at any point within 12 months from beginning of therapy are considered responders and all other patients are nonresponders.
Measured: Up to 48 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2020
- Study start18 Feb 2020
- Primary completion25 Feb 2025
- Study completion25 Feb 2025
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 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
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Subjects with Neurofibromatosis Type 2 (NF2) and progressive vestibular schwannoma (VS) will be treated with crizotinib administered orally. Crizotinib will be taken continuously until disease progression or unacceptable toxicity, in continuous treatment cycles of 28 days each, for a maximum of 12 cycles. Clinical response will be assessed by MRI (volumetrics, primary objective) and audiology at the end of every 3rd cycle. Subjects with volumetric tumor progression will be taken off protocol. Patients who complete 12 cycles of treatment without disease progression, but within the following 24 weeks show subsequent disease progression (defined as \>20% increase in target tumor volume compared to off-treatment volume), will be eligible for re-treatment on study for up to 48 additional weeks, provided they still meet study eligibility criteria.
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Girish Dhall, MD, University of Alabama at Birmingham
- Investigators
- Girish Dhall, MD, Study director, University of Alabama at BirminghamMatthias A Karajannis, MD, MS, Study chair, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04283669
- Sponsor's protocol ID
- IRB-300003645
- Other IDs
- W81XWH-17-2-0037
- Acronym
- NF110
- Status last verified
- Aug 2025
- First submitted
- 22 Feb 2020
- Last updated
- 13 Mar 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-label, Phase 2 Clinical Trial of Crizotinib for Children and Adults With Neurofibromatosis Type 2 and Progressive Vestibular Schwannomas
- ClinicalTrials.gov ID
- NCT04283669
- Acronym / sponsor ID
- NF110 / IRB-300003645
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Collaborators
- Memorial Sloan Kettering Cancer Center, Children's Hospital of Philadelphia
- Study start
- 18 Feb 2020 (actual)
- Primary completion
- 25 Feb 2025 (actual)
- Study completion
- 25 Feb 2025 (actual)
- First posted
- 25 Feb 2020 (actual)
- Results
- Posted 13 Mar 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Subjects with Neurofibromatosis Type 2 (NF2) and progressive vestibular schwannoma (VS) will be treated with crizotinib administered orally. Crizotinib will be taken continuously until disease progression or unacceptable toxicity, in continuous treatment cycles of 28 days each, for a maximum of 12 cycles.
Detailed description
Subjects with Neurofibromatosis Type 2 (NF2) and progressive vestibular schwannoma (VS) will be treated with crizotinib administered orally. Crizotinib will be taken continuously until disease progression or unacceptable toxicity, in continuous treatment cycles of 28 days each, for a maximum of 12 cycles. Clinical response will be assessed by MRI (volumetrics, primary objective) and audiology at the end of every 3rd cycle. Subjects with volumetric tumor progression will be taken off protocol. Patients who complete 12 cycles of treatment without disease progression, but within the following 24 weeks show subsequent disease progression (defined as >20% increase in target tumor volume compared to off-treatment volume), will be eligible for re-treatment on study for up to 48 additional weeks, provided they still meet study eligibility criteria.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Subjects with Neurofibromatosis Type 2 (NF2) and progressive vestibular schwannoma (VS) will be treated with crizotinib administered orally. Crizotinib will be taken continuously until disease progression or unacceptable toxicity, in continuous treatment cycles of 28 days each, for a maximum of 12 cycles. Clinical response will be assessed by MRI (volumetrics, primary objective) and audiology at the end of every 3rd cycle. Subjects with volumetric tumor progression will be taken off protocol. Patients who complete 12 cycles of treatment without disease progression, but within the following 24 weeks show subsequent disease progression (defined as >20% increase in target tumor volume compared to off-treatment volume), will be eligible for re-treatment on study for up to 48 additional weeks, provided they still meet study eligibility criteria.
| Arm | Type | Receives |
|---|---|---|
| Open Label Continuous Treatment | Other | Drug: CrizotinibSubjects with Neurofibromatosis Type 2 (NF2) and progressive vestibular schwannoma (VS) will be treated with crizotinib administered orally. Crizotinib will be taken continuously until disease progression or unacceptable toxicity, in continuous treatment cycles of 28 days each, for a maximum of 12 cycles. Clinical response will be assessed by MRI (volumetrics, primary objective) and audiology at the end of every 3rd cycle. Subjects with volumetric tumor progression will be taken off protocol. Patients who complete 12 cycles of treatment without disease progression, but within the following 24 weeks show subsequent disease progression (defined as >20% increase in target tumor volume compared to off-treatment volume), will be eligible for re-treatment on study for up to 48 additional weeks, provided they still meet study eligibility criteria. |
Who may qualify
- Ages
- 6 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (31 listed)
- Participants must meet the following criteria on screening examination to be eligible to participate in the study:
- 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.
- 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.
Key exclusion criteria (20 listed)
- Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study.
- Patients currently receiving medical anticancer therapies or who have received medical anticancer therapies within 4 weeks of the start of study drug (including chemotherapy and molecular targeted agents), as these may interfere with the study drug
- Monoclonal antibody treatment and/or agents with prolonged half-lives: At least three half-lives must have elapsed from the last dose prior to enrollment
- Radiation therapy to a study target tumor within 1 year prior to enrollment, or any radiation therapy within 4 weeks prior to enrollment, as these may interfere with our ability to assess response to study drug
- Prior treatment with any investigational drug within the preceding 4 weeks, as they may interfere with the study drug
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 |
|---|---|---|
| CrizotinibOral | Drug | Open Label Continuous Treatment |
Primary outcome
Volumetric Response Rate
Time frame: Up to 48 Weeks
To evaluate efficacy, imaging response is treated as a binary variable whereby patients who achieve a volumetric response (greater than 20% reduction in tumor volume) in the target tumor at any point within 12 months from beginning of therapy are considered responders and all other patients are nonresponders.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Girish Dhall, MD study director
University of Alabama at Birmingham
Matthias A Karajannis, MD, MS study chair
Memorial Sloan Kettering Cancer Center
15 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 Crizotinib in people with Neurofibromatosis 2 and Progressive Vestibular Schwannoma (VS), run by University of Alabama at Birmingham at 15 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 31 inclusion and 20 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 13 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 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 13 Mar 2026). 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?
Volumetric Response Rate (time frame: Up to 48 Weeks). 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 13 Mar 2026.