Phase II Study of Abraxane Plus Ipilimumab in Patients With Metastatic Melanoma

Inclusion Criteria: 1. Patients with histologically documented diagnosis of advanced stage IV or unresectable stage III mucosal or cutaneous melanoma are eligible. 2. They must have recurrent melanoma with measurable or evaluable sites of disease, 1.0 cm or larger, in order to assess the response to treatment by the immune-related response criteria (irRC). 3. Patients should not have been previously treated with cytotoxic drugs and immunotherapeutic agents for unresectable Stage III or Stage IV disease. Prior Ipilimumab in metastatic setting is not allowed. Prior therapy may include one line of targeted therapy for metastatic disease ie BRAF or MEK inhibitor. At least 3 weeks should have passed since the last dose of prior adjuvant interferon therapy and prior targeted therapies, and all previous therapy related toxicities should have resolved before starting study treatment. Prior adjuvant interferon is permitted. Prior cytotoxic therapy in adjuvant or metastatic setting is not allowed. Prior Ipilimumab in adjuvant setting is not allowed. Prior adjuvant therapy with targeted therapy including but not limited to B-RAF, MEK inhibitors etc. is allowed. Prior palliative radiation therapy for metastatic melanoma is permitted provided the patient has unirradiated metastatic sites for response evaluation and has fully recovered from its toxicity. 4. Patients between 12 years of age and 70 years of age with an ECOG performance status of 0 or 1 will be eligible 5. They should have normal blood counts with a white blood cell 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, Hemoglobin \> 9.0 g/dL 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 1.5 mg/dl, AST and ALT \</= 2.5X ULN unless presence of hepatic metastasis in which case AST and ALT \</= 5X ULN are acceptable. Alk Phos \</= 2.5X ULN ) 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), or active GI bleeding. 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 and signed informed consent . Exclusion Criteria: 1. Patients with metastatic uveal melanoma 2. Patients with bone metastases only. 3. Patients with symptomatic brain or spinal cord metastases or requiring steroid therapy and patients with leptomeningeal disease. Patients with treated and stable CNS metastasis for 3 months or more, off steroids are eligible for the study. 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 with significant history of cardiac disease will be evaluated by the investigator or his designee. 5. Patients with significant impairment of pulmonary function on account of chronic bronchitis, emphysema or chronic obstructive pulmonary disease (COPD) which has resulted in impairment of vital capacity of FEV1 to less than 75% 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. 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. 8. Patients with ≥ grade 2 sensory neuropathy at baseline. 9. Patients who have had major surgery or radiation therapy within 21 days of starting treatment.