Third Line TKI After 2 TKIs in Patients With mRCC (Tokio Study)

Inclusion Criteria: * Age ≥ 18 years * Patients with histological diagnosis of Renal Cell Carcinoma (RCC) * Measurable disease * Previous treatment with two sequences of TKIs including sunitinib followed by axitinib and pazopanib followed by sorafenib. * ECOG (Eastern Cooperative Oncology Group) Performance Status of 0 or 1 * All prognostic group according to Heng criteria * Life expectancy of at least 12 weeks. * Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening: * Hemoglobin \> or equal to 10.0 g/dl * Absolute neutrophil count (ANC) \>1,500/mm3 * Platelet count \> or equal to 100,000/ml * Total bilirubin ≤ 1.5 times the upper limit of normal * ALT (Alanine Transferase) and AST (Aspartate transferase) ≤ 2.5 x upper normal limit (ULN) * ALP (Alkaline phosphatase) ≤ 4 x ULN * PT-INR/PTT (Protrombine Time; International Normalized Ratio; Partial Tromboplastine Time)≤ 1.5 x upper limit of normal \[Patients who are being therapeutically anticoagulated with an agent such as coumadin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists.\] For patients on warfarin, close monitoring of at least weekly evaluations will be performed, until INR is stable based on a measurement at pre-dose, as defined by the local standard of care. * Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial and two weeks after the completion of trial. * Signed informed consent must be obtained prior to any study specific procedures Exclusion Criteria: * Previous treatment for metastatic RCC other than pazopanib followed by sorafenib or sunitinib followed by axitinib * History of cardiac disease: congestive heart failure \>NYHA class 2 (New York Heart Association); active CAD (MI more than 6 mo prior to study entry is allowed); cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension (\>= 160 mmHg systolic and/or 90 mmHg diastolic). * History of HIV infection * Active clinically serious infections (\> grade 2 NCI-CTC version 3.0) * Patients with seizure disorder requiring medication (such as steroids or anti-epileptics) * History of organ allograft * Patients with evidence or history of bleeding diathesis * Patients undergoing renal dyalisis * History of other disease, metabolic dysfunction, physical examination findings or clinical laboratory findings giving reasonable suspicion of a disease condition that contraindicates use of an investigational drug or patient at high risk from treatment complications * Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors \[Ta, Tis \& T1\] or any cancer curatively treated \> 2 years prior to study entry.