A Randomized Phase Ii Study Of Sunitinib Versus Dacarbazine In The Treatment Of Patients With Metastatic Uveal Melanoma.

TPS8605 Background: Metastatic uveal melanoma represents an orphan disease area with a median survival of less than 6 months. There is currently no effective systemic therapy for metastatic uveal melanoma and few clinical trials have been conducted. In the absence of phase III data, many patients in the UK continue to receive single agent dacarbazine or best supportive care outside of the context of clinical trials. Uveal melanoma is characterized by activation of the MAP kinase pathway via functionally activating mutations in Gnaq/11. Evidence also suggests that dysfunctional c-Kit signalling and angiogenesis may both play a role in disease progression and a small single-arm phase II trial recently reported preliminary activity using the multi-targeted receptor tyrosine kinase inhibitor, sunitinib (Tijani et al, ASCO 2010). Methods: The SUAVE trial aims to evaluate the Progression Free Survival (PFS) of good performance status patients treated with sunitinib or dacarbazine. Secondary objectives include: Overall Survival (OS), Overall Response Rate (ORR), safety, crossover PFS and response and biomarker analyses. SUAVE is a CR-UK-funded, open-label, randomised, phase II trial that will include 124 patients. Patients will be stratified according to their Helsinki Prognostic Index (ALP, largest diameter of largest metastasis, ECOG). Inclusion Criteria: good performance status patients with confirmed unresectable metastatic uveal melanoma, with at least one target lesion measurable by RECIST 1.1. Patients must not have received previous systemic therapy. At confirmed progression, good performance status patients may crossover to the other study treatment. The trial opened in Oct 2010 and as of 23 January 2012, had randomized 49 patients with at least 1 recruited from each of the 12 recruiting sites. There will be a total of 13 sites. Completion of the recruitment phase is expected within 36 months. Prospective tissue and blood sample collection for translational biomarker analyses is also ongoing. The SUAVE trial represents one of the largest randomised trials in this rare disease area (Clinical trial registry number: 2008-008794-55).