NEXT: Subsequent Exposure to Tyrosine Kinase Inhibition at Recurrence After Adjuvant Therapy in Renal Cell Carcinoma

Inclusion Criteria: * Locally recurrent or metastatic RCC requiring systemic therapy following treatment (tx) with sorafenib, sunitinib, pazopanib, or placebo on an adjuvant study * Required to have primary or recurrence tumor samples containing clear cell variant RCC with \<50% of any other histology * Recurrence must occur ≥ 3 months following end of exposure to the adjuvant intervention * Received ≥ 3 six week cycles of prior adjuvant tx with sorafenib, sunitinib, pazopanib or placebo in the adjuvant setting on a clinical trial, or recurrence \>3 months of tx on an adjuvant placebo arm * Required to have measurable recurrent or metastatic disease that is not curable by standard radiation therapy or surgery * Male or female, ≥ 18 years old * ECOG PS 0 or 1 * Blood pressure (B/P) must be controlled at time of enrollment. Tx with antihypertensive medication(s) is allowed. Controlled B/P is defined as in clinic measurement of systolic B/P ≤ 140 mm Hg AND diastolic B/P ≤ 90 mm Hg. If B/P is uncontrolled at time of planned enrollment, tx or optimization with antihypertensive medication(s) may be initiated in order to control B/P. Patient may be considered for enrollment when this has happened. * Women must not be pregnant or breastfeeding * Men and women who are of reproductive potential must be willing to employ an effective method of birth control/contraception * Willingness and ability to comply with scheduled visits, tx plans, laboratory tests, and other study procedures * Ability to understand and willingness to sign an IRB-approved informed consent * Adequate organ function as evidenced by the following, obtained within 28 days prior to registration: * Absolute neutrophil count (ANC) ≥ 1250 cells/mm³ * Platelet count ≥ 75,000 cells/mm³ * Hemoglobin ≥ 9.0 g/dL * Total direct serum bilirubin ≤ 1.5x upper limit of normal (ULN) * ALT and AST ≤ 2.5 x ULN unless there are liver metastases in which case AST and ALT ≤ 5.0 x ULN * Serum creatinine \<1.5 x ULN or calculated creatinine clearance ≥ 45 mL/min * Urine protein \<2+ by urine dipstick * Resolution of all previous tx-related toxicity to ≤ grade 1 or back to baseline * No major surgery \<4 weeks or radiation therapy \<2 weeks of starting study tx. Prior palliative radiotherapy to metastatic lesion(s) is permitted, provided there is at least one measurable lesion that has not been irradiated. * No clinically significant gastrointestinal abnormalities * No current use or anticipated need for tx with drugs that are known potent CYP3A4 inhibitors * No current or anticipated need for tx with drugs that are known CYP3A4 or CYP1A2 inducers * No current requirement of anticoagulant therapy with oral vitamin K antagonists * No untreated brain metastases, spinal cord compression, or carcinomatous meningitis. Patients must be off oral (systemic) steroids prior to registration. Inhalational steroids, e.g., for asthma, emphysema are permissible. * No serious uncontrolled medical disorder or active infection that would impair their ability to receive study tx * None of the following conditions within the 6 months prior to study drug: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, deep vein thrombosis or pulmonary embolism * No known HIV or AIDS-related illness * No other active malignancy * No dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of the protocol * No other severe acute/chronic medical or psychiatric condition or lab abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study