Intervention: Axitinib
Trial phase: Phase 2
ATC code: L01EK01 | L01XE17
SMILES: CNC(=O)c1ccccc1Sc1ccc2c(/C=C/c3ccccn3)n[nH]c2c1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 10
Group description: 5 mg axitinib orally twice daily, with increase to 7 mg orally twice daily and 10 mg orally twice daily after 2 and 4 weeks. Axitinib will be given continuously in 28-day cycles until disease progression or unacceptable toxicity.
Eligibility criteria:
Inclusion criteria

Age ≥18 years
Meets clinical diagnostic criteria for NF2
At least one volumetrically measurable and ≥1 cc NF2-related VS (histological confirmation not required)
MRI evidence of progression (either as >2 mm increase in maximum linear diameter on conventional MRI, or a >20%volume increase by 3D volumetrics) over the past ≤18 months, OR progressive hearing loss, defined as a decline in word recognition score below the 95% critical difference interval from baseline score related to VS (i.e., not due to prior interventions such as surgery or radiation)
Karnofsky performance status (PS) 60-100%. Note: Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
Adequate bone marrow function as shown by: absolute neutrophil count ≥1.5 x 10^9/L, Platelets ≥100 x 10^9/L, Hb >9 g/dL
Adequate liver function as shown by:
serum bilirubin ≤1.5 x upper limit of normal (ULN)
ALT and AST ≤2.5x ULN
INR ≤1.5. (anticoagulation with low molecular weight heparin is allowed if on a stable dose for >2 weeks at time of enrollment.)
Adequate renal function: serum creatinine ≤1.5 x ULN
Fully recovered from acute toxic effects of any prior chemotherapy, biological modifiers or radiotherapy
Any neurologic deficits must be stable for ≥1 week
Able to provide signed informed consent Exclusion criteria
Patients currently receiving medical anticancer therapies or who have received medical anticancer therapies within 4 weeks of the start of study drug (including chemotherapy, antibody based therapy, etc.)
Radiation therapy to a study target tumor within 1 year prior to enrollment, or any radiation therapy within 4 weeks prior to enrollment.
Patients who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patients that may require major surgery during the course of the study
Prior treatment with bevacizumab or other agents targeting vascular endothelial growth factor (VEGF) or VEGF receptor
Prior treatment with any investigational drug within the preceding 4 weeks
Unstable or rapidly progressive disease, including patients who require glucocorticoids for symptomatic control of brain or spinal tumors
Treatment with strong CYP3A4 enzyme inhibitors or inducers, including but not limited to ketoconazole, itraconazole, ritonavir, phenytoin, carbamazepine, rifampin, rifabutin, phenobarbital and St. John's wort
Requirement of therapeutic anticoagulant therapy with oral vitamin K antagonists; low-dose anticoagulants for maintenance of patency of central venous access devise or prevention of deep venous thrombosis is allowed; therapeutic use of low molecular weight heparin (or similar parenteral drug) for venous-thromboembolic disease is allowed.
Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin.
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 diffusion capacity of lung for carbon monoxide (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 axitinib (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
Patients with an active bleeding diathesis
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 8 weeks after the last dose of study drug, by both sexes. (Females of childbearing potential must have a negative serum pregnancy test within 7 days prior to administration of axitinib)
Male patient whose sexual partner(s) are women of child bearing potential, who are not willing to use adequate contraception, during the study and for 8 weeks after the end of treatment
History of noncompliance to medical regimens
Patients unwilling to or unable to comply with the protocol