A Study of the Effect of Food on the Pharmacokinetics of Single Dose RO5185426 And the Safety And Efficacy of Continuous Administration in Patients With BRAF V600E Mutation-Positive Metastatic Melanoma

A Phase I, Randomized, Open-label, Multi-center, Two Period Crossover Study to Investigate the Effect of Food on the Pharmacokinetics of a Single Oral Dose of RO5185426, Followed by Administration of 960 mg RO5185426 Twice Daily to BRAF V600E Positive Metastatic Melanoma Patients

This randomized, open-label, two period crossover study will evaluate the effect of food on the pharmacokinetics of a single dose of RO5185426 and the efficacy and safety of continuous administration in patients with BRAF V600E mutation-positive metastatic melanoma. Patients will be randomized to receive in a crossover design single oral doses of RO5185426 with or without food, with a 10-day washout period between doses. Following the crossover periods, patients will receive RO5185426 orally twice daily on a continuous basis until disease progression or unacceptable toxicity occurs.

Inclusion Criteria:

• Adult patients, >/= 18 years of age
• Histologically confirmed metastatic melanoma (Stage IV, American Joint Committee on Cancer)
• Positive BRAF V600E mutation result determined by Cobas 4800 BRAF V600 Mutation Test
• Previously treated patients must have failed at least one prior treatment regimen; if patients have received prior systemic treatments for metastatic melanoma, the time elapsed from previous therapy must be >/= 28 days; patients must have recovered fully from toxicities of all prior therapy
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Evaluable disease (measurable for disease progression according to RECIST criteria)
• Adequate hematological, renal and liver function

Exclusion Criteria:

• Active CNS lesions
• History of or known spinal cord compression or carcinomatous meningitis
• Anticipated or ongoing administration of anti-cancer therapies other than those administered in this study
• Previous malignancy within the past 5 years except for basal or squamous cell carcinoma of the skin, melanoma in-situ and carcinoma in-situ of the cervix
• Previous treatment with BRAF inhibitor (sorafenib allowed) or MEK inhibitor
• Refractory nausea or vomiting, malabsorption, external biliary shunt, or history of any type of gastrointestinal surgery that would preclude adequate absorption of study drug