A Study of Tivozanib (AV-951), an Oral VEGF Receptor Tyrosine Kinase Inhibitor, in the Treatment of Renal Cell Carcinoma

Inclusion Criteria: * ≥ 18 year old males or females * Patients with recurrent or metastatic renal cell carcinoma (RCC) or primary RCC that is not amendable to surgical intervention * Histologically or cytologically confirmed renal cell carcinoma * Measurable disease * No more than one prior systemic treatment (chemotherapy or immunotherapy) for RCC. * No active brain metastases * Karnofsky performance status ≥ 70%, life expectancy ≥ 3 months * No childbearing potential, or use of effective contraception during the study and for 4 weeks after the last dose of study drug * Archival paraffin embedded tumor tissue, if available. * Ability to give written informed consent Exclusion Criteria: * Pregnant or lactating women * Primary CNS malignancies; active CNS metastases * Hematologic malignancies (includes: leukemia, any form; lymphoma; and multiple myeloma) * Any of the following hematologic abnormalities: * Hemoglobin ≤ 9.0 g/dL * ANC \< 1500 per mm3 * Platelet count \< 100,000 per mm3 * Any of the following serum chemistry abnormalities: * Total bilirubin \> 1.5 × the ULN * AST or ALT ≥ 2.5 × the ULN * Serum albumin \< 3.0 g/dL * Creatinine \> 1.7 × ULN (or calculated CLCR \<50 mL/min/1.73 m2) * Proteinuria \> 2.5 g/24 hours or 4+ with urine dipstick * Significant cardiovascular disease, including: * Active clinically symptomatic left ventricular failure * Active HTN (diastolic blood pressure \> 100 mmHg). Patients with a history of hypertension must have been on stable doses of anti-hypertensive drugs for ≥ 4 weeks * Uncontrolled hypertension: Blood pressure \>140/90 mmHg on more than 2 antihypertensive medications. * Myocardial infarction within 3 months prior to administration of first study dose * Unhealed wounds (including active gastric ulcers) * Serious/active infection; infection requiring parenteral antibiotics * Inadequate recovery from prior antineoplastic therapy * Inadequate recovery from any prior surgical procedure; major surgical procedure within 4 weeks prior to study entry * Life-threatening illness or organ system dysfunction compromising safety evaluation * Psychiatric disorder, altered mental status precluding informed consent or necessary testing * Inability to comply with protocol requirements