Randomized, Double-Blind Phase III Study of Pazopanib vs. Placebo in Patients With Metastatic Renal Cell Carcinoma Who Have No Evidence of Disease Following Metastatectomy

Inclusion Criteria:

- Patient must have pathologically confirmed renal cell carcinoma with a clear cell
component; pure papillary and chromophobe histologies are excluded; there must be
pathologic confirmation of metastatic disease in the resected metastasectomy specimen

- Patient must have undergone nephrectomy or partial nephrectomy to remove primary
renal cell carcinoma (at any time in the past)

- Patient must have undergone surgical resection to remove one or more sites of
metastatic disease, with successful removal of all known sites 2-12 weeks prior to
randomization

- Eligible patient must have no evidence of disease on post-operative imaging (computed
tomography [CT] and/or magnetic resonance imaging [MRI]) conducted within 4 weeks
prior to randomization

- Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of
0 or 1 at the time of randomization

- Absolute granulocyte count > 1,500/mcL

- Platelets > 100,000/mcL

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

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT])
< 2.5 times upper limit of normal (ULN)

- Calculated creatinine clearance (CrCl) > 30 mL/min

- Women must not be pregnant or breast-feeding

- All females of childbearing potential must have a blood test or urine study
within 2 weeks prior to randomization to rule out pregnancy; a female of
childbearing potential is any woman, regardless of sexual orientation or whether
they have undergone tubal ligation, who meets the following criteria: has not
undergone a hysterectomy or bilateral oophorectomy; or has not been naturally
postmenopausal for at least 24 consecutive months (i.e., has had menses at any
time in the preceding 24 consecutive months)

- Women of childbearing potential and sexually active males must be strongly advised to
use an accepted and effective method of contraception or to abstain from sexual
intercourse for the duration of their participation in the study

- Patient must be able to swallow pills and have no significant impairment in
gastrointestinal absorption including history of gastric bypass surgery

- Patient must have no history of allergic reactions attributed to compounds of similar
chemical or biologic composition to pazopanib

- Patient must have no uncontrolled intercurrent illness including, but not limited to,
ongoing or active infection, symptomatic congestive heart failure, unstable angina
pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would
limit compliance with study requirements

- Patient must have a QTc interval on electrocardiogram (ECG) =< 0.48 seconds by
Bazett's calculation (=< Common Terminology Criteria for Adverse Events [ CTCAE] v.4
Grade 2) prior to randomization

- Patient must have a systolic blood pressure =<140 mm Hg and diastolic blood pressure
must be =< 90 mm Hg, measured within 4 weeks prior to randomization; initiation or
adjustment of anti-hypertensives prior to starting study treatment is allowed

- Patient must not have serious or non-healing wound, ulcer, or bone fracture at the
time of randomization

- Patient must have no history of abdominal fistula, gastrointestinal perforation, or
intra-abdominal abscess within 4 weeks prior to randomization

- Patient must have no history of cerebrovascular accident (CVA) within 6 months of
randomization

- Patient must have no history of myocardial infarction, hospital admission for
unstable angina, cardiac angioplasty, or stenting within 6 months of randomization

- Patient must have no history of venous thrombosis within 12 weeks of randomization

- Patient must not have history of hemoptysis in excess of 2.5 mL (½ teaspoon) within
8weeks prior to randomization

- Patient must be able to receive either computed tomography (CT) with intravenously
(IV) contrast or magnetic resonance imaging (MRI) with gadolinium

- Patient must not have received any prior or concurrent systemic therapy for RCC;
adjuvant placebo administration is permitted

- Patient cannot be taking strong CYP3A4 inhibitors such as:

- Antibiotics: clarithromycin, telithromycin, troleandomycin

- Human immunodeficiency virus (HIV) antiviral protease inhibitors: ritonavir,
indinavir, saquinavir, nelfinavir, amprenavir, lopinavir

- Antifungals: itraconazole, ketoconazole, voriconazole, fluconazole

- Antidepressants: nefazodone

- Patient must not be taking drugs known to prolong the QTc interval; such drugs should
be discontinued at least 1 week prior to randomization