This is a single-arm, two-stage, Phase II clinical trial to test the safety and effectiveness of an investigational treatment, the combination of ipilimumab and nivolumab with cryoablation, for the treatment of metastatic melanoma resistant to PD-1 inhibition.~Ipilimumab and nivolumab are types of inhibitors. Ipilimumab targets and blocks specific proteins in cancer cells which are responsible for stopping the immune system from working correctly. Nivolumab targets a receptor on cancer cells that causes programmed cell death.~The U.S. Food and Drug Administration has approved Ipilimumab and Nivolumab for the treatment of melanoma.~Cryoablation is an approved procedure that consists of freezing a tumor and surgically removing it. The use of the study drugs and cryoablation combination is experimental.~Study procedures including screening for eligibility, study treatment including in-clinic visits, blood sample collections, Computerized Tomography (CT) scans, and tumor biopsies.~Participation in this research study is expected to last up to 3 years.~It is expected that about 37 people will take part in this research study.~The William M. Wood Foundation is supporting this research by providing funding for the cryoablation and research activities.
The aim of this study is to find out whether the combination of two approved drugs, ipilimumab and nivolumab, in combination with cryoablation are safe and effective for participants who have an unresectable melanoma that is resistant, or is growing, after receiving immunotherapy with a PD-1 inhibitor.~The names of the study interventions involved in this study are:~Cryoablation (an interventional radiology procedure that freezes part of a tumor)~Ipilimumab (an immunotherapy)~Nivolumab (an immunotherapy)