Parallel (Randomized) Phase II Evaluation of ARQ 197 and ARQ 197 in Combination With Erlotinib in Papillary Renal Cell Carcinoma

PRIMARY OBJECTIVES: I. To assess the response rate (confirmed complete and partial response) of patients with locally advanced or metastatic papillary renal cell carcinoma treated with either ARQ 197 (tivantinib) or ARQ 197 combined with erlotinib (erlotinib hydrochloride). SECONDARY OBJECTIVES: I. To assess the progression free survival (PFS) of patients with locally advanced or metastatic papillary renal cell carcinoma treated with either ARQ 197 or ARQ 197 combined with erlotinib. II. To assess the safety and tolerability of ARQ 197 therapy and ARQ 197 combined with erlotinib. III. To descriptively assess the role of prior treatment on outcome. TERTIARY OBJECTIVES: I. To bank tissue specimens for future use and once funding is obtained to evaluate the expression of tissue correlative biomarkers such as hepatocyte growth factor receptor (c-MET) and epidermal growth factor receptor (EGFR), and to perform exploratory correlation with clinical outcomes. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive tivantinib orally (PO) twice daily (BID) on days 1-28. ARM II: Patients receive tivantinib PO BID and erlotinib hydrochloride PO once daily (QD) on days 1-28. In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months for up to 2 years.