Everolimus Post Pazopanib Treatment in Metastatic or Advanced Renal Cell Carcinoma (CATChEz)

Inclusion Criteria:

1. Written informed consent
2. Diagnosis of renal cell carcinoma with clear-cell component histology.
3. Locally advanced/metastatic renal cell carcinoma
4. Measurable lesion (RECIST 1.1) on physical exam or as CT/MRI
5. No prior systemic therapy for advanced/metastatic RCC
6. Karnofsky performance scale >=70
7. Age >=18 years
8. A female is eligible to enter and participate in this study if she is of: non-childbearing/agrees to use adequate contraception
9. A male with female partner of childbearing potential must have vasectomy/agree to use effective contraception from two weeks prior to administration of the 1st dose of study treatment for a period of time after the last dose of study treatment
10. Adequate organ function
11. Able to swallow and retain orally administered medication and must not have clinically significant GIT abnormalities that may alter absorption

Exclusion Criteria:

1. Pregnant/lactating
2. History of another malignancy (unless have been disease-free for 3 years)
3. History or clinical evidence of Central nervous system metastases (unless have previously-treated CNS metastases and who meet both of the following criteria: a) are asymptomatic and b) have no requirement for steroids or enzyme-inducing anticonvulsants in prior 6 month time interval.
4. Clinically significant gastrointestinal abnormalities including, but not limited to: malabsorption syndrome, major resection of the stomach or small bowel that could affect the absorption of study drug, active peptic ulcer disease, known intraluminal metastatic lesion/s with suspected bleeding, Inflammatory bowel disease, ulcerative colitis, or other gastrointestinal conditions with increased risk of perforation, history of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess
5. Moderate to severe hepatic impairment (Child-Pugh Class C)
6. Any serious and/or unstable pre-existing medical, psychiatric, or other conditions that could interfere with patient's safety, obtaining informed consent or compliance to the study.
7. Subjects receiving chronic treatment with corticosteroids/other immunosuppressive agents
8. Subjects with a known history of HIV seropositivity
9. Subjects with active bleeding, bleeding diathesis or on oral anti-vitamin K medication (except low dose coumadin)
10. Presence of any severe or uncontrolled medical conditions/infection.
11. Currently receiving chemotherapy, immunotherapy or radiotherapy
12. Corrected QT interval (QTc) > 480 milliseconds
13. History of any one or more of the following cardiovascular conditions within the past 12 months: cardiac angioplasty or stenting, myocardial infarction, unstable angina, coronary artery by-pass graft surgery, symptomatic peripheral vascular disease, Class III or IV congestive heart failure, as defined by the New York Heart Association
14. Poorly controlled hypertension (defined as systolic blood pressure of >=140mmHg or diastolic blood pressure of >=90mmHg).
15. History of cerebrovascular accident including transient ischemic attack, pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months (unless recent DVT have been treated with therapeutic anti-coagulating agents for at least 6 weeks)
16. Major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer.
17. Evidence of active bleeding or bleeding susceptibility
18. Use of an investigational agent, including an investigational anti-cancer agent, within 30 days or 5 half-lives, whichever is longer, prior to the first dose of study drug.
19. Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is progressing in severity, except alopecia.
20. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib or everolimus, to other rapamycin derivatives or to any other excipients.