Systemic Therapy With Interferon, Interleukin-2 and BRAF Inhibitor

Inclusion Criteria:

1. Patients with histologically documented diagnosis of advanced stage IV or unresectable stage III skin or mucosal melanoma are eligible if they have BRAF mutation affecting the V600 site, as determined by a chemiluminescence immunoassay analyzer (CLIA)-certified assay. Mutation testing of archival tumor tissue is acceptable, or it may be performed on new biopsy. If a new biopsy is performed for testing, biopsy of a metastasis is preferred to biopsy of a primary tumor.
2. Patients must have at least one bidimensionally measurable lesion. If this is a cutaneous lesion it must be at least 10 mm by caliper measure. If it is a visceral or nodal or soft tissue lesion, it must be clearly measurable \> 20 mm with conventional techniques or \> 10 mm with spiral CT scan. Bone lesions are not considered measurable.
3. Phase I: Patients with prior therapy who do not have alternative treatment of higher priority will be eligible. Phase II: the patient may have been treated with cytotoxic drugs or targeted therapies for metastatic disease but not with IL-2, interferon and BRAF inhibitor drugs. Adjuvant interferon will be permitted. Prior radiation therapy for metastatic melanoma is permitted provided the patient has unirradiated metastatic sites for response evaluation and has fully recovered from its toxicity. Prior chemotherapy is permitted provided the patient has a 21 day wash out period and the patient has fully recovered from its toxicity.
4. Patients between 18 years of age and 65 years of age with an Eastern Cooperative Oncology (ECOG) performance status of 0, 1 or 2 will be eligible.
5. They should have normal blood counts with a white blood cell count (WBC) count of more than or equal to 3000/mm\^3 an absolute neutrophil count of more than or equal to 1500/mm\^3 and a platelet count of more than 100,000/mm\^3 and have no impairment of renal function (serum creatinine less than 1.1 mg/dl for females and less than 1.4 mg/dl for males), hepatic function (serum bilirubin level of less than 1.2 mg/dl) and no evidence of significant cardiac or pulmonary dysfunction.
6. They should have no significant intercurrent illness such as an active infection associated with fever lasting more than 24 hours requiring antibiotics, uncontrolled psychiatric illness, hypercalcemia (calcium greater than 11 mg), active GI bleeding, myocardial disease with corrected QT interval (QTC) interval \> 480 on baseline ECG or history of rheumatoid arthritis.
7. Females of child-bearing potential (non-childbearing is defined as greater than one year post-menopausal or surgically sterilized) must use acceptable contraceptive methods( abstinence, intrauterine device, oral contraceptive or double barrier devices) and must have a negative serum or urine pregnancy test within 72 hours prior to beginning treatment on this trial. Sexually active men must also use acceptable contraceptive methods for the duration of time on study.

Exclusion Criteria:

1. Patients with uveal melanoma.
2. Patients with bone metastases only.
3. Patients with brain metastases unless all of their metastatic brain lesions have been resected or treated with stereotactic radiotherapy with gamma rays and they are off corticosteroids. Patient should not have significant brain edema. Patients with spinal cord compression and leptomeningeal disease. No major surgery or radiation therapy within 21 days before starting treatment.
4. Patients with significant cardiac illness such as symptomatic coronary artery disease or previous history of myocardial infarction, impaired left ventricle function (Ejection Fraction less than 50%) on account of any organic disease such as hypertension or valvular heart disease or serious cardiac arrhythmia requiring therapy. Patients will be evaluated by the investigator or his designee.
5. Patients with significant impairment of pulmonary function on account of chronic bronchitis or chronic obstructive pulmonary disease (COPD) which has resulted in impairment of vital capacity of forced expiratory volume at one second (FEV1) to less than 65 % of predicted normal values.
6. Patients with symptomatic effusions on account of pleural, pericardial or peritoneal metastases of melanoma.
7. Patients who are unable to return for follow-up visits as required by this study.
8. Patients with a history of second malignant tumor, other than the common skin cancers - basal and squamous carcinomas, within the past 3 years and uncertainty about the histological nature of the metastatic lesions. Cases with other types of malignancies should be reviewed and decided by the PI of the study.