This is an open-label, dose finding, multiple-dose study in subjects with metastatic melanoma. Three dose levels of MPC-6827 will be administered with temozolomide to three separate cohorts. Study endpoints will include determination of the maximum tolerated dose, determination of dose limiting toxicities, and evaluation of evidence of anti-tumor activity of MPC-6827 when given with temozolomide.

Inclusion Criteria:

• Histologically proven melanoma
• For subjects with brain metastases that require radiation, therapy must have been completed at least 4 weeks prior to Day 1 of Study Drug
• Have unresectable melanoma with measurable metastases
• Be a minimum of 4 weeks since prior surgical resection or major surgical procedure and a minimum of 2 weeks since chemotherapy/ biochemotherapy
• Performance score of Karnofsky ≥ 60%, or Eastern Cooperative Oncology Group (ECOG) ≤ 2, or WHO ≤ 2
• If steroids are needed, be on a stable or decreasing dose of steroids for at least 1 week

Exclusion Criteria:

• Hypersensitivity to Cremophor EL
• Have current/active intratumor hemorrhage by CT/MRI within 3 weeks prior to Day 1 of Study Drug confirmed by CT/MRI
• Have ocular melanoma
• Have primary intradural melanoma or leptomeningeal involvement
• Have cardiovascular disease (unstable angina or MI)
• Have cerebrovascular disease (stroke and/or TIA)
• Have uncontrolled hypertension
• Have a cardiac ejection fraction < 50%
• Have Troponin-I elevated above the normal range