This study is being performed to prospectively determine whether dacarbazine plus Genasense is significantly better than dacarbazine plus placebo in chemotherapy-naive patients with advanced melanoma and low baseline LDH (LDH less than or equal to 0.8 times the upper limit of normal). LDH is a biomarker strongly associated with improved outcomes in a recent trial of dacarbazine plus Genasense.

Inclusion Criteria:

• Histologically confirmed diagnosis of melanoma
• Progressive disease that is not surgically resectable, or metastatic Stage IV
• Low-normal LDH, defined as ≤ 0.8 times the upper limit of normal
• No prior chemotherapy
• Measurable disease
• ECOG performance status ≤ 1
• At least 4 weeks and recovery from effects of major prior surgery or other therapy, including immunotherapy, radiation therapy, or cytokine, biologic or vaccine therapy
• Prior immunotherapy allowed
• Adequate organ function

Exclusion Criteria:

• Prior cytotoxic chemotherapy, including regional perfusion, or prior Genasense treatment
• Primary ocular or mucosal melanoma
• Bone-only metastatic disease
• History or presence of brain metastasis or leptomeningeal disease
• Significant medical disease other than cancer
• Organ allograft