Continuous selumetinib versus continuous or interrupted selumetinib in combination with weekly paclitaxel in metastatic uveal melanoma

INTERVENTION: 1. Paclitaxel, IMP 2. Selumetinib, IMP CONDITION: Topic: Cancer; Subtopic: Melanoma; Disease: Melanoma ; Cancer PRIMARY OUTCOME: Progression Free Survival (PFS) time.; Timepoint(s): Progression SECONDARY OUTCOME: 1. GNAQ/GNA11 mutation status; 2. RECIST Response; 3. Safety and toxicity INCLUSION CRITERIA: Histologically or cytologically confirmed metastatic uveal melanoma 1. Patients must have measurable disease, defined by RECIST 1.1 2. Age at least18 years 3. ECOG performance status 0­2 4. Life expectancy of greater than 3 months 5. Able to swallow and retain orally­administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels 6. All prior treatment­related toxicities must be CTCAE v4 grade = 1 (except alopecia) at the time of randomization 7. Laboratory values as listed below (SI units): 7.1. Total bilirubin = 1.5 X institutional upper limit of normal (ULN) 7.2. Aspartate aminotransferase or alanine aminotransferase >2.5 x ULN (or =5 ULN in presence of liver metastases) 7.3. Haemoglobin =9.0 g/dL 7.4. Platelets >100x109/L (100,000 per mm3) 7.5. Absolute neutrophil count >1.5x109/L (1500 p