Testing Cabozantinib, Crizotinib, Savolitinib and Sunitinib in Kidney Cancer Which Has Progressed

PRIMARY OBJECTIVE: I. To compare progression-free survival (PFS) in patients with metastatic papillary renal cell carcinoma (mPRCC) treated with sunitinib malate (sunitinib) to PFS in patients with mPRCC treated with MET kinase inhibitors. SECONDARY OBJECTIVES: I. To compare Response Evaluation Criteria in Solid Tumors (RECIST) response rate (RR; defined as the combined rate of confirmed and unconfirmed partial response \[PR\] and confirmed and unconfirmed complete response \[CR\]) in patients with mPRCC treated with sunitinib to RR in patients treated with putative MET inhibitors. II. To compare overall survival (OS) in patients with mPRCC treated with sunitinib to OS in patients with mPRCC treated with putative MET inhibitors. III. To compare the safety profile of sunitinib and putative MET inhibitors in patients with mPRCC. TRANSLATIONAL OBJECTIVES: I. To evaluate the prognostic and predictive value of MET mutations, MET copy number or other markers of MET signaling in patients with mPRCC treated with putative MET inhibitors. II. To estimate the frequency of high oncometabolite levels in formalin-fixed, paraffin-embedded (FFPE) tissues of patients with advanced papillary renal cell carcinoma by liquid chromatography-mass spectrometry (LC-MS/MS) and estimate progression free survival for those with and without high oncometabolite levels being treated. III. To correlate the mutational signature suggestive of a homologous recombination defect with high oncometabolite levels in patients with papillary renal cell carcinoma pRCC. OUTLINE: Patients are randomized to 1 of 4 treatment arms. As of 12/5/18, patients will only be randomized to Arm I or Arm II. ARM I: Patients receive sunitinib malate orally (PO) once daily (QD) on days 1-28. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) at screening and on study, undergo bone scan as clinically indicated, and undergo collection of plasma and serum samples at screening, on study, and during follow up. ARM II: Patients receive cabozantinib s-malate PO QD on days 1-42. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT at screening and on study, undergo bone scan as clinically indicated, and undergo collection of plasma and serum samples at screening, on study, and during follow up. ARM III (CLOSED TO ACCRUAL 12/5/18): Patients receive crizotinib PO twice daily (BID) on days 1-42. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT at screening and on study, undergo bone scan as clinically indicated, and undergo collection of plasma and serum samples at screening, on study, and during follow up. ARM IV (CLOSED TO ACCRUAL 12/5/18): Patients receive savolitinib PO QD on days 1-42. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT at screening and on study, undergo bone scan as clinically indicated, and undergo collection of plasma and serum samples at screening, on study, and during follow up. After completion of study treatment, patients are followed up for 3 years.