Phase I/II Trial of Valproic Acid and Karenitecin for Melanoma

Treatment cycles are every 3 weeks and there are 17 study visits in all. During Phase I subjects will receive one cycle of Karenitecin alone (cycle 1 days 1-5) and then combination therapy with VPA + Karenitecin (cycle 2 days 1-7)followed by oral VPA in divided doses for 5 days and Karenitecin starting the third day (days 3-7) every 3 weeks. After 2 cycles of treatment there will be the first efficacy evaluation or restaging of the disease. Dose escalations will continue until unacceptable dose limiting toxicity (DLT) occurs, then dose escalation will be stopped and the previous dose level will be explored. In each dose level, participants will undergo pharmacokinetic (PK) sampling to determine blood levels. The melanoma skin lesions will also be biopsied to measure the effect of the combination therapy. All patients enrolled in the Phase II will be treated with VPA and Karenitecin using the dosing schedule determined to be the MTD in Phase I. In the absence of disease progression and if there is continued safety and tolerability, treatment may continue in consecutive 3 week cycles.