A Pilot Clinical Trial of Neoadjuvant Tivozanib in Localized Renal Cell Carcinoma

Inclusion Criteria:

- Biopsy proven non-metastatic clear cell RCC, as per radiographic studies is T2 - T3a
based on the American Joint Committee on Cancer (AJCC) 6th edition criteria

- Have an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2

- Hemoglobin >= 10 gm/dL

- Absolute neutrophil count (ANC) >= 1.5 X 10^9/L

- Platelets >= 100 X 10^9/L

- Total bilirubin < 1.5 X upper limit of normal (ULN)

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 X ULN

- International normalization ratio (INR) < 1.5

- Activated partial thromboplastin time (aPTT) < 1.2 X ULN

- Serum creatinine < 1.5 mg/dL or if >= 1.5 mg/dL: calculated creatinine clearance
(CrCL) > 30 mL/min based on Cockroft-Gault formula

- Must have the ability to swallow and retain oral medication

- Patients of childbearing potential must agree to use acceptable contraceptive methods
(e.g., double barrier) during treatment

- Patient or legal representative must understand the investigational nature of this
study and sign an Independent Ethics Committee/Institutional Review Board approved
written informed consent form prior to receiving any study related procedure

Exclusion Criteria:

- Pregnant or nursing female patients

- Unwilling or unable to follow protocol requirements

- Any condition which in the Investigator's opinion deems the patient an unsuitable
candidate to receive tivozanib (solitary kidney, multiple tumors in the same or
contralateral kidney)

- Not a candidate for surgery

- Received an investigational agent within 30 days prior to enrollment

- Non-clear cell or sarcomatoid histology

- Patients with metastatic disease at presentation

- Prior therapy with tyrosine kinase inhibitor for RCC

- A second primary malignancy (except squamous and basal cell carcinoma of skin) in the
past 3 years

- Active or chronic infections

- Significant cardiovascular disease, including:

- Clinically symptomatic left ventricular failure

- Uncontrolled hypertension: systolic blood pressure of > 150 mmHg or diastolic
blood pressure of > 100 mmHg documented on 2 consecutive measurements taken at
least 24 hours apart

- Myocardial infarction, severe angina, or unstable angina within 6 months prior
to administration of first dose of tivozanib

- History of serious ventricular arrhythmia (i.e., ventricular tachycardia or
ventricular fibrillation)

- Cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial
fibrillation that is well controlled with anti-arrhythmic medication)

- Coronary or peripheral artery bypass graft within 6 months of screening

- History of coronary artery disease or peripheral arterial disease

- History of stroke or carotid endarterectomy

- Patients who are taking cytochrome P450 system (CYP)3A4 inducers are excluded;
patients taking CYP3A4 inducers that can be safely replaced with another agent may be
enrolled after a 5 day washout period