A Phase II Study of Nilotinib in Growing Vestibular Schwannomas

UHN laboratory has demonstrated that targets of Imatinib (c-Kit and PDGFR-α and PDGFR-ß) are overexpressed and activated in both sporadic and NF2 VS.It has also been shown pre-clinically that Imatinib induced a reduction in proliferation and cell viability, with increased apoptosis, in HEI-193 human NF2-null VS cells.Nilotinib is a newer generation RTK inhibitor, with a similar target profile as Imatinib. It was designed by modifying the Imatinib molecule62, and has 30-fold increased potency compared to IImatinib43. In clinical studies of patients with CML or GIST resistant to Imatinib, Nilotinib has demonstrated efficacy with minimal toxicity. Nilotinib (Tasigna®, code number AMN107) was first approved in 2007 for use in Philadelphia chromosome positive CML in the chronic or accelerated phase in patients resistant or intolerant to prior therapy. Thus making Nilotinib an ideal drug to study in understanding its benefit in VS patients.