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