Nivolumab With and Without Ipilimumab and Radiation Therapy in Treating Patients With Recurrent or Resectable Undifferentiated Pleomorphic Sarcoma or Dedifferentiated Liposarcoma Before Surgery

PRIMARY OBJECTIVES: I. To assess the pathologic response of nivolumab monotherapy and nivolumab and ipilimumab combination therapy administered in the neoadjuvant setting with and without radiation in patients with treatment-naive primary or locally recurrent resectable undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma. SECONDARY OBJECTIVES: I. To assess the change in percent viable tumor cells, percent hyalinization and necrosis, proliferation by phosphohistone H3 in biopsy specimens obtained at baseline and on treatment and surgical specimens. II. To assess the change in immune infiltrate in response to neoadjuvant nivolumab monotherapy and neoadjuvant nivolumab and ipilimumab combination therapy in patients with resectable undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma. III. To assess the objective response rate (ORR) of nivolumab monotherapy and nivolumab and ipilimumab combination therapy administered in the neoadjuvant setting as assessed by imaging (Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1 and Immune Related Response Criteria \[irRC\]) in patients with resectable undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma. IV. To assess the 12- and 24-month recurrence-free survival (RFS) and overall survival (OS) of patients with resectable undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma treated with neoadjuvant nivolumab monotherapy or nivolumab and ipilimumab combination therapy. V. To evaluate the safety of nivolumab monotherapy and combination ipilimumab and nivolumab in the neoadjuvant setting and peri-operatively by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 criteria. EXPLORATORY OBJECTIVES: I. To identify immunologic and genomic markers correlating with clinical response to nivolumab monotherapy and ipilimumab with nivolumab combination therapy. II. To assess the quality of life of patients with dedifferentiated liposarcoma and undifferentiated pleomorphic sarcoma undergoing neoadjuvant immunotherapy followed by surgical resection. III. To analyze the microbiome to determine the role of the microbiome on development and response to therapy. OUTLINE: Patients are randomized to 1 of 4 arms. ARM A: Patients receive nivolumab intravenously (IV) over 1 hour on days 1, 15, and 29 in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery within 2 weeks after day 43. ARM B: Patients receive nivolumab as in Arm A. Patients also receive ipilimumab IV over 90 minutes on day 1 in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery within 2 weeks after day 43. ARM C: Patients receive nivolumab IV over 1 hour on days 1, 15, 29, and 43. Patients also undergo radiation therapy (RT) once daily (QD) for 5 days during days 15-47 in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery within 2 weeks after day 71. ARM D: Patients receive nivolumab as in Arm C, ipilimumab as in Arm B, and RT as in Arm C in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery within 2 weeks after day 71. After completion of study treatment, patients are followed up at 6 and 18 weeks and then every 3 months for up to 2 years.