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