Concurrent Ipilimumab and Stereotactic Ablative Radiation Therapy (SART) for Oligometastatic But Unresectable Melanoma

Primary Objectives: 1. To evaluate the effectiveness of concurrent ipilimumab therapy and SART of melanoma based on 1-year and 2-year overall survival. 2. To evaluate the safety and tolerability of concurrent ipilimumab therapy and SART of melanoma based on CTCAE grading of toxicities, and to identify any novel or unexpected Grade 3 or 4 toxicities thought specifically related to ipilimumab and concurrent SART during first 3 cycles of ipilimumab therapy (prior to week 9) in a Phase II study. Secondary Objectives: 1. To evaluate the 1-year and 2-year disease control rates (CR+PR+SD) 2. Assess treatment response based on Immune Related Response Criteria (irRC) and mWHO criteria. 3. Characterize overall survival by Kaplan-Meier analysis. Exploratory Objectives: 1. Evaluate individual lesion control (\<25% progression) following body SART at 6, 12, 24 months. 2. Describe number of patients requiring retreatment of any local lesion with surgery or other treatments. 3. Describe the incidence of new brain metastases following ipilimumab therapy. 4. Describe the incidence of treatment related toxicity and/or symptomatic bleeding, perforation, or necrosis at SART treated tumor sites. 5. Explore the use of circulating melanoma cells and serum metastasis gene expression levels as prognostic and predictive (intermediate) markers to identify responding patients. 6. Assess the effect of therapy on quality of life, using ECOG score as a surrogate. Study Rationale: Ipilimumab may markedly enhance the immunologic responses to tumor antigen released from necrotic tumor cells by radiotherapy by promoting cytotoxic T cell activation, while preventing induction of antigen tolerance. In addition, further beneficial immunologic effects may be achieved by the reduction in the amount of viable tumor cell mass. The net effect may be to promote a significantly enhanced antitumor T cell response. This will result in improved 1-year and 2-year survival, especially if a minimal or microscopic disease state can be achieved within a patient following SART. Biologic Correlation Studies: There are currently no standard prognostic or predictive markers to evaluate or predict outcome of ipilimumab therapy. This study provides the opportunity for exploratory analysis of several candidate hypotheses that may predict outcome.