Neoadjuvant Pazopanib: A Phase II Study to Evaluate the Effect on Disease Response and Recurrence and to Establish Predictive Biomarkers of Drug Activity in Renal Cell Carcinoma

Inclusion Criteria:

- Age ≥ 18 years with radiographic evidence of nonmetastatic renal cell carcinoma

- Histological verification of clear cell renal cell carcinoma (-Clinical stage 2 (7
cm) or greater with localized disease

- No evidence of extranodal metastatic disease

- Appropriate candidate for surgery

- ECOG Performance status of 0-1

- Adequate organ function

- Serum calcium, magnesium, potassium within normal limits

- No known coagulopathy

- Ability to read and follow instructions

- Women of childbearing potential must have a negative serum pregnancy test performed
within 14 days prior to the start of pazopanib treatment and both men and women must
be willing to use adequate contraception.

- Able to provide written, informed consent

- Blood and urine samples must be provided from all subjects for biomarker analysis
before and during treatment with pazopanib

Exclusion Criteria

- Known or suspected allergy to pazopanib

- Inability to swallow or retain oral medication

- Prior malignancy Exception: Subjects who have had another malignancy and have been
disease-free for three years, or subjects with a history of completely resected
non-melanomatous skin carcinoma or successfully treated in situ carcinoma are
eligible.

- Unable or unwilling to discontinue use of prohibited medications at least 7 days
prior to the first dose of study drug and for the duration of the study.

- Clinically significant gastrointestinal abnormalities that may increase the risk for
gastrointestinal bleeding including

- History of cerebrovascular accident including transient ischemic attack (TIA),
pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6
months.

- History of any one or more cardiovascular conditions within the past 6 months

- Hypertension [defined as systolic blood pressure (SBP) of ≥140 mmHg OR diastolic
blood pressure (DBP) of ≥ 90mmHg in spite of optimal medical management.

- Evidence of active bleeding or bleeding diathesis.

- Any serious and/or unstable pre-existing medical (especially hepatic disease),
psychiatric, or other condition that could interfere with subject's safety, provision
of informed consent, or compliance to study procedures.

- Prior major surgery or trauma within 28 days prior to first dose of pazopanib and/or
presence of any non-healing wound, fracture, or ulcer (procedures such as catheter
placement not considered to be major).

- Pregnant or breastfeeding; breastfeeding may not resume for 14 days after the last
dose of pazopanib

- Prior treatment with any of the following anti-cancer therapies for treatment of
their RCC:

- radiation therapy, surgery or tumor embolization

- chemotherapy, immunotherapy, biologic therapy, investigational therapy or
hormonal therapy

- Baseline QTc>480 msec or other clinically significant baseline ECG abnormality