Pilot Study of Pazopanib With Low Fat Meal (PALM) in Advanced Renal Cell Carcinoma

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.