Neoadjuvant Pazopanib in Renal Cell Carcinoma

The primary objective of this study is to determine the objective response rate Complete Response + Partial Response(CR+PR) associated with neoadjuvant pazopanib at 8 weeks as defined via Response Evaluation Criteria in Solid Tumors (RECIST1.1). The investigators will also estimate the recurrence free survival (RFS), specifically the 1 and 2 year rates, with recurrence defined via RECIST1.1, and characterize the safety issues. Finally, this study also includes a number of exploratory analyses designed to evaluate potential correlations between RFS and; serum levels of cytokine and angiogenesis factor (CAF).

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
• The Eastern Cooperative Oncology Group (ECOG) Performance status of 0-1
• Adequate organ function
• Serum calcium, magnesium, potassium within normal limits, or if outside of normal limits, must be deemed clinically insignificant by the Investigator.
• 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 ≥ 90 mmHg 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 Corrected QT Interval (QTc) >480 msec or other clinically significant baseline ECG abnormality