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.