Pazopanib is an orally administered multi-kinase inhibitor targeting VEGFR (vascular endothelial growth factor receptor), PDGFR (platelet derived growth factor) and c-kit, which are critical to growth and proliferation of neoplastic cells. Pazopanib has been FDA approved for advanced renal cell carcinoma (RCC) with a clear cell component. Conventional Pazopanib dosing WITHOUT FOOD is with an initial dose of 800 mg by mouth daily. Investigators hypothesize that administration of pazopanib with low fat meal would be safe and feasible with secondary implications of higher pazopanib levels; potentially translating into greater anti-tumor efficacy in advanced renal cell cancer, with significant cost savings. In the proposed pilot study, investigators seek to test the feasibility and practicality of this approach and gather preliminary data on adverse effects and the safety profile. Investigators hope to ameliorate any potential for greater toxicities with a dynamic dosing design that incorporates adverse events from each cycle into dosing for the next cycle and a structured symptom specific plan.

Inclusion Criteria:

• Adult (>18 years of age) with unresectable locally advanced or metastatic renal cell carcinoma with a clear cell component.
• Subjects must have measurable disease per RECIST 1.1 criteria.
• Subjects must not have had prior pazopanib therapy.
• Subjects must have an ECOG (Eastern Cooperative Oncology Group scoring system used to quantify general well-being and activities of daily life; scores range from 0 to 5 where 0 represents perfect health and 5 represents death.) performance status of less than or equal to 2.
• Up to 3 lines of prior VEGF (vascular endothelial growth factor) or VEGFR (vascular endothelial growth factor receptor) targeted therapy are permitted. Any prior therapy should have been completed ≥ 2 weeks prior to start of study therapy.
• Subjects may have received any number of the following therapies: cytokine therapy (e.g. high dose interleukin-2) or checkpoint inhibitor therapy (e.g. anti-PD1/PDL1, anti-CTLA4) or mTOR inhibitor therapy (e.g. everolimus, temsirolimus).
• Adequate organ and marrow function (Absolute neutrophil count > 1000/mm3, platelets > 100,000/mm3, aspartate aminotransferase/ alanine aminotransferase/ total bilirubin < 1.5 X ULN (upper limit of normal). Patients with Gilbert's disease are exempt.
• Subject must be willing and able to take pazopanib with a low-fat meal every day as specified in the protocol.
• Subjects must be willing and able to come off any PPI(proton pump inhibitor)/other strong CYP3A4 inhibitors or inducers/simvastatin.
• Ability to understand and the willingness to sign a written informed consent.
• All subjects, including those who are surgically sterilized, must be willing to use an effective method of contraception.

Exclusion Criteria:

• Any concurrent health condition that in the view of the treating physician would pose excessive risk to the patient if enrolled in the study.
• Subjects with a history of hemoptysis, cerebral hemorrhage, clinically significant GI hemorrhage, myocardial infarction within the past 6 months.
• Patients at significant risk for GI (gastrointestinal) perforation or fistula.
• Pregnant or nursing mothers.
• Untreated CNS (central nervous system) metastasis. If treated CNS metastasis/es, treatment of CNS disease (surgery or radiation) must have been completed at least 30 days prior to registration. Patients could still be on steroids.
• Subjects with known history of Cirrhosis, HIV, Hepatitis B or C.
• Averaged QTc baseline in 3 ECGs (electrocardiograms) at least 5 minutes apart of ≥450 ms.
• Congestive Heart Failure (NYHA Class III/IV) or LVEF (left ventricular ejection fraction) <50% at baseline.
• Uncontrolled hypertension (HTN) despite medical management (blood pressure (BP) ≥ 160/100.

Sixteen patients were enrolled in this study; three patients withdrew study consent prior to study completion.

Through 12 weeks of treatment up to 30 days post last treatment administration

Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.