Trial Outcomes & Findings for Phase 2 Clinical Trial of Crizotinib for Children and Adults With Neurofibromatosis Type 2 and Progressive Vestibular Schwannomas (NCT NCT04283669)
NCT ID: NCT04283669
Last Updated: 2026-03-13
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
12 participants
Primary outcome timeframe
Up to 48 Weeks
Results posted on
2026-03-13
Participant Flow
2 participants were enrolled in error, and 1 participant did not receive study treatment.
Participant milestones
| Measure |
Open Label Continuous Treatment
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.
Crizotinib: Oral
|
|---|---|
|
Overall Study
STARTED
|
9
|
|
Overall Study
COMPLETED
|
4
|
|
Overall Study
NOT COMPLETED
|
5
|
Reasons for withdrawal
| Measure |
Open Label Continuous Treatment
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.
Crizotinib: Oral
|
|---|---|
|
Overall Study
Progressive Disease
|
5
|
Baseline Characteristics
Phase 2 Clinical Trial of Crizotinib for Children and Adults With Neurofibromatosis Type 2 and Progressive Vestibular Schwannomas
Baseline characteristics by cohort
| Measure |
Open Label Continuous Treatment
n=9 Participants
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.
Crizotinib: Oral
|
|---|---|
|
Age, Continuous
|
16.8 years
n=41 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=41 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=41 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=41 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=41 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=41 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=41 Participants
|
|
Race (NIH/OMB)
White
|
8 Participants
n=41 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=41 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=41 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
4 Participants
n=41 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
5 Participants
n=41 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=41 Participants
|
PRIMARY outcome
Timeframe: Up to 48 WeeksPopulation: Analysis population consists of 9 participants that received the study treatment.
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.
Outcome measures
| Measure |
Open Label Continuous Treatment
n=9 Participants
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.
Crizotinib: Oral
|
|---|---|
|
Volumetric Response Rate
Responders
|
0 Participants
|
|
Volumetric Response Rate
Non-responders
|
9 Participants
|
Adverse Events
Open Label Continuous Treatment
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Open Label Continuous Treatment
n=9 participants at risk
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.
Crizotinib: Oral
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
11.1%
1/9 • The study period during which all AEs and SAEs must be reported begins after the time of first dose of study drug. The reporting period for both AEs and SAEs ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier. After this period, investigators should only report SAEs that are attributed to prior study treatment.
|
|
Ear and labyrinth disorders
Tinnitus
|
22.2%
2/9 • The study period during which all AEs and SAEs must be reported begins after the time of first dose of study drug. The reporting period for both AEs and SAEs ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier. After this period, investigators should only report SAEs that are attributed to prior study treatment.
|
|
Eye disorders
Blurred vision
|
11.1%
1/9 • The study period during which all AEs and SAEs must be reported begins after the time of first dose of study drug. The reporting period for both AEs and SAEs ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier. After this period, investigators should only report SAEs that are attributed to prior study treatment.
|
|
Eye disorders
Extraocular muscle paresis
|
11.1%
1/9 • The study period during which all AEs and SAEs must be reported begins after the time of first dose of study drug. The reporting period for both AEs and SAEs ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier. After this period, investigators should only report SAEs that are attributed to prior study treatment.
|
|
Eye disorders
Eye Disorders - Other, Astrocytic Retinal Hamartomas
|
11.1%
1/9 • The study period during which all AEs and SAEs must be reported begins after the time of first dose of study drug. The reporting period for both AEs and SAEs ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier. After this period, investigators should only report SAEs that are attributed to prior study treatment.
|
|
Eye disorders
Eye Disorders - Other, Shutter Like Effect
|
11.1%
1/9 • The study period during which all AEs and SAEs must be reported begins after the time of first dose of study drug. The reporting period for both AEs and SAEs ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier. After this period, investigators should only report SAEs that are attributed to prior study treatment.
|
|
Eye disorders
Eye Disorders - Other, Vision Changes
|
11.1%
1/9 • The study period during which all AEs and SAEs must be reported begins after the time of first dose of study drug. The reporting period for both AEs and SAEs ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier. After this period, investigators should only report SAEs that are attributed to prior study treatment.
|
|
Gastrointestinal disorders
Constipation
|
11.1%
1/9 • The study period during which all AEs and SAEs must be reported begins after the time of first dose of study drug. The reporting period for both AEs and SAEs ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier. After this period, investigators should only report SAEs that are attributed to prior study treatment.
|
|
Gastrointestinal disorders
Diarrhea
|
77.8%
7/9 • The study period during which all AEs and SAEs must be reported begins after the time of first dose of study drug. The reporting period for both AEs and SAEs ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier. After this period, investigators should only report SAEs that are attributed to prior study treatment.
|
|
Gastrointestinal disorders
Dyspepsia
|
33.3%
3/9 • The study period during which all AEs and SAEs must be reported begins after the time of first dose of study drug. The reporting period for both AEs and SAEs ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier. After this period, investigators should only report SAEs that are attributed to prior study treatment.
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
11.1%
1/9 • The study period during which all AEs and SAEs must be reported begins after the time of first dose of study drug. The reporting period for both AEs and SAEs ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier. After this period, investigators should only report SAEs that are attributed to prior study treatment.
|
|
Gastrointestinal disorders
Gastrointestinal Disorders - Other, Abdominal Cramping
|
11.1%
1/9 • The study period during which all AEs and SAEs must be reported begins after the time of first dose of study drug. The reporting period for both AEs and SAEs ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier. After this period, investigators should only report SAEs that are attributed to prior study treatment.
|
|
Gastrointestinal disorders
Gastrointestinal Disorders - Other, Geographic Tongue
|
11.1%
1/9 • The study period during which all AEs and SAEs must be reported begins after the time of first dose of study drug. The reporting period for both AEs and SAEs ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier. After this period, investigators should only report SAEs that are attributed to prior study treatment.
|
|
Gastrointestinal disorders
Nausea
|
44.4%
4/9 • The study period during which all AEs and SAEs must be reported begins after the time of first dose of study drug. The reporting period for both AEs and SAEs ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier. After this period, investigators should only report SAEs that are attributed to prior study treatment.
|
|
Gastrointestinal disorders
Vomiting
|
55.6%
5/9 • The study period during which all AEs and SAEs must be reported begins after the time of first dose of study drug. The reporting period for both AEs and SAEs ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier. After this period, investigators should only report SAEs that are attributed to prior study treatment.
|
|
General disorders
Fatigue
|
11.1%
1/9 • The study period during which all AEs and SAEs must be reported begins after the time of first dose of study drug. The reporting period for both AEs and SAEs ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier. After this period, investigators should only report SAEs that are attributed to prior study treatment.
|
|
General disorders
Gait disturbance
|
11.1%
1/9 • The study period during which all AEs and SAEs must be reported begins after the time of first dose of study drug. The reporting period for both AEs and SAEs ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier. After this period, investigators should only report SAEs that are attributed to prior study treatment.
|
|
General disorders
Non-cardiac chest pain
|
11.1%
1/9 • The study period during which all AEs and SAEs must be reported begins after the time of first dose of study drug. The reporting period for both AEs and SAEs ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier. After this period, investigators should only report SAEs that are attributed to prior study treatment.
|
|
Infections and infestations
Nail infection
|
11.1%
1/9 • The study period during which all AEs and SAEs must be reported begins after the time of first dose of study drug. The reporting period for both AEs and SAEs ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier. After this period, investigators should only report SAEs that are attributed to prior study treatment.
|
|
Infections and infestations
Otitis media
|
11.1%
1/9 • The study period during which all AEs and SAEs must be reported begins after the time of first dose of study drug. The reporting period for both AEs and SAEs ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier. After this period, investigators should only report SAEs that are attributed to prior study treatment.
|
|
Infections and infestations
Paronychia
|
11.1%
1/9 • The study period during which all AEs and SAEs must be reported begins after the time of first dose of study drug. The reporting period for both AEs and SAEs ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier. After this period, investigators should only report SAEs that are attributed to prior study treatment.
|
|
Infections and infestations
Skin infection
|
11.1%
1/9 • The study period during which all AEs and SAEs must be reported begins after the time of first dose of study drug. The reporting period for both AEs and SAEs ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier. After this period, investigators should only report SAEs that are attributed to prior study treatment.
|
|
Investigations
Alanine aminotransferase increased
|
33.3%
3/9 • The study period during which all AEs and SAEs must be reported begins after the time of first dose of study drug. The reporting period for both AEs and SAEs ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier. After this period, investigators should only report SAEs that are attributed to prior study treatment.
|
|
Investigations
Alkaline phosphatase increased
|
22.2%
2/9 • The study period during which all AEs and SAEs must be reported begins after the time of first dose of study drug. The reporting period for both AEs and SAEs ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier. After this period, investigators should only report SAEs that are attributed to prior study treatment.
|
|
Investigations
Aspartate aminotransferase increased
|
22.2%
2/9 • The study period during which all AEs and SAEs must be reported begins after the time of first dose of study drug. The reporting period for both AEs and SAEs ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier. After this period, investigators should only report SAEs that are attributed to prior study treatment.
|
|
Investigations
CPK increased
|
11.1%
1/9 • The study period during which all AEs and SAEs must be reported begins after the time of first dose of study drug. The reporting period for both AEs and SAEs ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier. After this period, investigators should only report SAEs that are attributed to prior study treatment.
|
|
Investigations
Creatinine increased
|
11.1%
1/9 • The study period during which all AEs and SAEs must be reported begins after the time of first dose of study drug. The reporting period for both AEs and SAEs ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier. After this period, investigators should only report SAEs that are attributed to prior study treatment.
|
|
Investigations
Weight gain
|
11.1%
1/9 • The study period during which all AEs and SAEs must be reported begins after the time of first dose of study drug. The reporting period for both AEs and SAEs ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier. After this period, investigators should only report SAEs that are attributed to prior study treatment.
|
|
Metabolism and nutrition disorders
Anorexia
|
11.1%
1/9 • The study period during which all AEs and SAEs must be reported begins after the time of first dose of study drug. The reporting period for both AEs and SAEs ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier. After this period, investigators should only report SAEs that are attributed to prior study treatment.
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
33.3%
3/9 • The study period during which all AEs and SAEs must be reported begins after the time of first dose of study drug. The reporting period for both AEs and SAEs ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier. After this period, investigators should only report SAEs that are attributed to prior study treatment.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
11.1%
1/9 • The study period during which all AEs and SAEs must be reported begins after the time of first dose of study drug. The reporting period for both AEs and SAEs ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier. After this period, investigators should only report SAEs that are attributed to prior study treatment.
|
|
Musculoskeletal and connective tissue disorders
Fracture
|
11.1%
1/9 • The study period during which all AEs and SAEs must be reported begins after the time of first dose of study drug. The reporting period for both AEs and SAEs ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier. After this period, investigators should only report SAEs that are attributed to prior study treatment.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorder - Other, Bilateral Hip Pain
|
11.1%
1/9 • The study period during which all AEs and SAEs must be reported begins after the time of first dose of study drug. The reporting period for both AEs and SAEs ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier. After this period, investigators should only report SAEs that are attributed to prior study treatment.
|
|
Nervous system disorders
Acoustic nerve disorder NOS
|
11.1%
1/9 • The study period during which all AEs and SAEs must be reported begins after the time of first dose of study drug. The reporting period for both AEs and SAEs ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier. After this period, investigators should only report SAEs that are attributed to prior study treatment.
|
|
Nervous system disorders
Facial nerve disorder
|
11.1%
1/9 • The study period during which all AEs and SAEs must be reported begins after the time of first dose of study drug. The reporting period for both AEs and SAEs ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier. After this period, investigators should only report SAEs that are attributed to prior study treatment.
|
|
Nervous system disorders
Headache
|
11.1%
1/9 • The study period during which all AEs and SAEs must be reported begins after the time of first dose of study drug. The reporting period for both AEs and SAEs ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier. After this period, investigators should only report SAEs that are attributed to prior study treatment.
|
|
Nervous system disorders
Paresthesia
|
22.2%
2/9 • The study period during which all AEs and SAEs must be reported begins after the time of first dose of study drug. The reporting period for both AEs and SAEs ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier. After this period, investigators should only report SAEs that are attributed to prior study treatment.
|
|
Nervous system disorders
Trigeminal nerve disorder
|
11.1%
1/9 • The study period during which all AEs and SAEs must be reported begins after the time of first dose of study drug. The reporting period for both AEs and SAEs ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier. After this period, investigators should only report SAEs that are attributed to prior study treatment.
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
11.1%
1/9 • The study period during which all AEs and SAEs must be reported begins after the time of first dose of study drug. The reporting period for both AEs and SAEs ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier. After this period, investigators should only report SAEs that are attributed to prior study treatment.
|
|
Skin and subcutaneous tissue disorders
Skin And Subcutaneous Tissue Disorders - Other, Rash
|
11.1%
1/9 • The study period during which all AEs and SAEs must be reported begins after the time of first dose of study drug. The reporting period for both AEs and SAEs ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier. After this period, investigators should only report SAEs that are attributed to prior study treatment.
|
|
Skin and subcutaneous tissue disorders
Skin infection
|
11.1%
1/9 • The study period during which all AEs and SAEs must be reported begins after the time of first dose of study drug. The reporting period for both AEs and SAEs ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier. After this period, investigators should only report SAEs that are attributed to prior study treatment.
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
11.1%
1/9 • The study period during which all AEs and SAEs must be reported begins after the time of first dose of study drug. The reporting period for both AEs and SAEs ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier. After this period, investigators should only report SAEs that are attributed to prior study treatment.
|
|
Metabolism and nutrition disorders
Metabolism and nutrition disorders - Other, Hyperchloremia
|
22.2%
2/9 • The study period during which all AEs and SAEs must be reported begins after the time of first dose of study drug. The reporting period for both AEs and SAEs ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier. After this period, investigators should only report SAEs that are attributed to prior study treatment.
|
Additional Information
Faculty Statistician, Neurofibromatosis Data Coordinating Center
Children's Hospital of Philadelphia
Phone: 2674253084
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place