N-cadherin, a protein involved in blood vessel cell binding and on the surface of many tumor cells, is increased as cancer progresses. ADH-1 blocks N-cadherin. This study will test the safety and effects of the combination ADH-1 with Normothermic Isolated Limb Infusion of Melphalan in subjects with locally advanced malignant melanoma.

Inclusion Criteria:

• Signed written informed consent
• Male and female patients > or = 18 years of age with diagnosis of melanoma for which treatment with Normothermic Isolated Limb Infusion (ILI) of melphalan would be appropriate
• Measurable disease
• Disease site(s) must be distal to the planned site of tourniquet placement
• Available for immunohistochemical testing of N-cadherin expression tumor tissue
• Adequate performance status and organ function, as evidenced by hematological and biochemical blood testing and ECG

Exclusion Criteria:

• Receipt of ADH-1 prior to this clinical study (prior melphalan via ILI, is okay)
• Stage IV melanoma
• Chemotherapy, radiotherapy, or any other investigational drug within 4 weeks before study entry
• History of tumors that have shown clinically significant evidence of active bleeding within 12 weeks before study entry
• Stroke, major surgery, or other major tissue injury within 4 weeks before study entry
• Uncontrolled congestive heart failure, coronary artery disease, or life threatening arrhythmias; myocardial infarction within 12 months; significant electrocardiogram (ECG) abnormalities
• Allergic reaction to any therapeutic peptide or to melphalan