A Study to Compare Treatments for a Type of Kidney Cancer Called TFE/Translocation Renal Cell Carcinoma (tRCC)

PRIMARY OBJECTIVE: I. To establish the clinical activity, assessed primarily by progression-free survival, of nivolumab therapy with or without axitinib for advanced transcription factor E3/translocation morphology renal cell carcinoma (TFE/tRCC). SECONDARY OBJECTIVE: I. To further define the toxicities of the study arms in the treatment of translocation morphology RCC across all ages. EXPLORATORY OBJECTIVES: I. To characterize tRCC clinical behavior across all age groups. II. To evaluate type of antitumor immune response and stability of T cell activation before and after treatment with immunotherapy or antiangiogenic therapy. III. To develop a tumor bank of tRCC tumor samples treated on study for further biological investigations. IV. To characterize the pharmacokinetics of axitinib when given in combination with nivolumab in pediatric patients with tRCC. OUTLINE: Patients are now randomized to 1 of 2 arms - Arm A or Arm C. ARM A: Patients receive axitinib orally (PO) twice daily (BID) on days 1-28 and nivolumab intravenously (IV) over 30 minutes, or per institutional guidelines, on days 1 and 15 (if \< 18 years old) or on day 1 (if \>= 18 years old). Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive axitinib PO BID on days 1-28. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. (CLOSED TO ACCRUAL AS OF 1/23/2020 - PROSPECTIVE PATIENTS ARE RANDOMLY ASSIGNED TO ARMS A OR C) ARM C: Patients receive nivolumab IV over 30 minutes, or per institutional guidelines, on days 1 and 15 (if \< 18 years old) or on day 1 (if \>= 18 years old). Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for 1 year, and every 6 months for 2 years. Follow-up at year 5 and beyond is at the discretion of the treating physician.