CRUK/12/020: PIANO - A Phase II Trial of PLX3397 in KIT Mutant Acral and Mucosal Melanoma

Background: Heterogeneous activating mutations in c-KIT occur in 10-15% of acral and mucosal melanomas. Inhibitors of c-KIT such as imatinib have shown efficacy in c-KIT mutant advanced melanoma and currently we are leading the CRUK-funded NICAM trial of nilotinib in c-KIT mutant melanoma. This trial is due to close to recruitment late in 2012. Aims: We propose here a follow-up Phase II trial of the potent c-KIT inhibitor PLX3397 in the same patient group. This drug was developed by Plexxikon Inc using their proprietary technology which was used in the development of the BRAF inhibitor PLX4032 (now vemurafenib), the first ever targeted agent to show a progression-free and overall survival benefit in BRAF mutant advanced melanoma. An important goal of the proposed study will be to increase our understanding of the biology of response and resistance to anti-c-KIT therapy in melanoma in collaboration with Professor Richard Marais. Methods: Two stage phase II design with translation endpoints based on tumour biopsies and circulating tumour cell analysis. How Results May Be Used: To increase understanding of activity of and safety of PLX3397 in c-KIT mutant melanoma and biology of response and resistance.