This research study is testing the "chemo-switch" strategy in melanoma, using biochemotherapy initially to shrink tumors and then switching to daily low-dose chemotherapy (temozolomide) together with sorafenib. The purpose of this study is to find out what effects (good and bad) biochemotherapy followed by temozolomide plus sorafenib have on melanoma.

Inclusion Criteria:

• Must have histologically or cytologically confirmed melanoma that is locally advanced or metastatic. Cutaneous, mucosal, ocular, and unknown primary melanoma are all eligible.
• Must have measurable disease, defined by RECIST as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20mm with conventional techniques or >10mm with spiral CT scan.
• May have received prior radiation therapy to one or more non-index lesions (prior radiation to an index lesion is allowable only if progression of the irradiated lesion is demonstrated, with progression defined as an increase of 20% or more in the largest diameter) and/or one prior vaccine therapy for metastatic disease. Prior adjuvant therapy with IFN alpha-2b, vaccine, and/or granulocyte-macrophage colony-stimulating factor (GM-CSF) is permitted. At least 4 weks must have elapsed since the completion of any prior therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Patients must have normal organ and marrow function as defined below:
• leukocytes >3,000/uL (microliters)
• absolute neutrophil count >1,500/uL
• platelets >100,000/uL
• total bilirubin <2.0mg/dL
• AST (Aspartate transaminase)(SGOT)/ALT (Alanine transaminase)(SGPT) <2.5 X institutional upper limit of normal
• creatinine <1.8mg/dL
• If >50 years of age with one or more cardiac risk factors, must demonstrate normal exercise stress test, stress thallium test, or comparable cardiac ischemia evaluation.
• Must be at least 2 weeks out from major surgery and be free of any active infection requiring antibiotics.
• Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation. Women must demonstrate a negative pregnancy test prior to initiation of protocol therapy.
• Ability to understand and the willingness to sign a written informed consent form.

Exclusion Criteria:

• Prior chemotherapy, cytokine therapy (including IL-2 or IFN alpha), or antibody therapy for metastatic disease. Prior vaccine therapy is permitted.
• May not be currently receiving any other antineoplastic treatments, including chemotherapy, biologic response modifiers, radiation, vaccine, or investigational agents.
• History of brain metastases.
• Autoimmune disorders that could result in life-threatening complications in the setting of IFN alpha and IL-2 treatment.
• History of sensitivity to E. coli-derived products.
• Concurrent use of corticosteroids or any medical condition likely to require the use of systemic corticosteroids.
• A seizure disorder currently requiring anti-epileptic medication.
• Uncontrolled intercurrent illness including, but not limited to, hypertension, active infection requiring antibiotic therapy, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Evidence of bleeding diathesis.
• Currently on therapeutic anticoagulation. Prophylactic anticoagulation (such as low-dose warfarin) of venous or arterial access devices is allowed provided the PT, PTT (Partial Thromboplastin Time), and international normalized ratio (INR) are normal.