Vorinostat in Treating Patients With Metastatic or Unresectable Melanoma

Inclusion Criteria: * Histologically/cytologically confirmed melanoma that is metastatic/unresectable * Residual, recurrent, or metastatic disease by radiographic examination. Measurable disease (at least 1 lesion in at least 1 dimension (longest diameter) as \>20mm with conventional techniques or \>10mm with spiral CT scan, within 4 weeks prior to registration * No prior therapy or 1 prior treatment (cytokine/chemotherapy/combination) for metastatic disease allowed. Patients should not take valproic acid, another histone deacetylase inhibitor, for at least 2 weeks prior to enrollment. At least 4 weeks from prior therapy to be eligible or 6 weeks if last regimen included BCNU or mitomycin C * Age\>=18 years * Life expectancy \>=3 months. * ECOG\<2 (Karnofsky ≥60%) * Leukocytes \>3,000/mcL * Absolute neutrophil count \>1,500/mcL * Platelets \>100,000/mcL * Total bilirubin within institutional limits * AST/ALT≤2.5Xinstitutional ULN * Creatinine within institutional limits OR creatinine clearance \>60mL/min/1.73 m2 if creatinine levels above institutional limits * Eligibility of patients taking medications with potential to affect activity/PK of Vorinostat will be determined by PI * Must not use concomitant steroids except topical/inhaled use * Vorinostat effects on developing human fetus are unknown. Women of childbearing potential (WOCBP) and sexually active males must agree to use accepted/effective contraception method prior to study entry and for duration of the study * Ability to understand/willingness to sign written informed consent * Must have paraffin block of tumor tissue available for future studies Exclusion Criteria: * Chemotherapy/radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering study * May not be receiving any other investigational agents * Known brain metastases * History of allergic reactions attributed to compounds of similar chemical/biologic composition to Vorinostat * Uncontrolled intercurrent illness including but not limited to ongoing/active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * Pregnant women excluded because Vorinostat is a HDAC inhibitor agent with potential for teratogenic or abortifacient effects * HIV-positive patients receiving combination antiretroviral therapy are ineligible because of potential for PK interactions with Vorinostat