8527 Background: The preliminary results for 90 patients (pt) on this 4-arm phase II trial testing sorafenib (SO), an oral Raf kinase/VEGFR2 inhibitor, and temozolomide (TEM) in pt with metastatic melanoma (MM) were presented in 2006. Since then 88% of target accrual is completed and the study is open at a second institution. The primary objective of this study is to estimate the duration of progression- free survival (PFS). Secondary objectives are to determine the optimal dosing of TEM, response, and toxicity rates. Correlative studies include BRAF genotyping and assessment of intratumoral Raf inhibition, and apoptosis. Methods: Pt with MM and ECOG PS<2 are eligible. Prior therapy is allowed. Target accrual is 167 pt in 1 stage. All pt receive SO 400 mg po bid continuously. After 1 week of SO alone, pt without brain metastasis or prior TEM (A+B) are randomized to receive either extended dosing (ED): TEM 75 mg/m2 po qd for 6/8 weeks (Arm A), or standard dosing (STD): TEM 150 mg/m2 po qd for days1–5/28 (A...