Efficacy and Safety Comparison of RAD001 Versus Sunitinib in the First-line and Second-line Treatment of Patients With Metastatic Renal Cell Carcinoma

Exclusion Criteria

• •1. Less than 4 weeks post-major surgery
• •2. Patients who had radiation therapy within 4 weeks prior to start of study treatment (palliative radiotherapy to bone lesions allowed within 2 weeks prior to study treatment start).
• •3. Patients in need for major surgical procedure during the course of the study
• •4. Patients with a serious non-healing wound, ulcer, or bone fracture
• •5. Patients with a history of seizure(s) not controlled with standard medical therapy
• •6. Patients who have received prior systemic treatment for their metastatic RCC
• •7. Patients who have previously received systemic mTOR inhibitors (sirolimus, temsirolimus, everolimus) or VEGF inhibitors. Note: History of adjuvant immunotherapy, vaccines or adjuvant sorafenib following localized surgical nephrectomy is acceptable.
• •8. Patients with a known hypersensitivity to RAD001 (everolimus) or other rapamycins (sirolimus, temsirolimus) or to its excipients Patients with a known hypersensitivity to RAD001 (everolimus) or other rapamycins or to its excipients
• •9. Patients with a known hypersensitivity to sunitinib or its excipients
• •10. History or clinical evidence of central nervous system (CNS) metastases. Note: Subjects who have previously-treated CNS metastases (surgery plus or minus radiotherapy, radiosurgery, or gamma knife) and meet all 3 of the following criteria are eligible:
• •* Are asymptomatic and,
• •* have had no evidence of active CNS metastases for ≥ 6 months prior to enrollment and,
• •* have no requirement for steroids or enzyme-inducing anticonvulsants (EIAC)
• •11. 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
• •* Inflammatory bowel disease
• •* Ulcerative colitis, or other gastrointestinal conditions with increased risk of perforation
• •* History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment.
• •12. Poorly controlled hypertension \[defined as systolic blood pressure (SBP) of ≥160mmHg or diastolic blood pressure (DBP) of ≥ 95mmHg\]
• •13. Patients receiving chronic systemic treatment with corticosteroids or another immunosuppressive agent
• •14. Patients with a known history of HIV seropositivity.
• •15. Patients with active bleeding.
• •16. Patients who have any severe and/or uncontrolled medical conditions or other conditions within the past 12 months that could affect their participation in the study such as:
• •* Cardiac angioplasty or stenting, unstable angina pectoris, symptomatic peripheral vascular disease, symptomatic congestive heart failure (NYHA II, III, IV), myocardial infarction ≤ 6 months prior to first study treatment, serious uncontrolled cardiac arrhythmia, cerebrovascular accidents ≤ 6 months before study treatment start.
• •* Prolongation of corrected QT interval (QTc) \> 500 milliseconds (msecs).
• •* Severally impaired lung function as defined as spirometry and DLCO that is 50% of the normal predicted value and/or 0\^2 saturation that is 88% or less at rest on room air.
• •* Poorly controlled diabetes as defined by fasting serum glucose \>2.0 x ULN.
• •* Any active (acute or chronic) or uncontrolled infection/disorders that impair the ability to evaluate the patient or for the patient to complete the study.
• •* Liver disease such as chronic active hepatitis or chronic persistent hepatitis.
• •17. History of cerebrovascular accident (CVA) including transient ischemic attack (TIA).
• •18. History of pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months. Note: Subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible.
• •19. Patients who have a history of another primary malignancy and off treatment for ≤ 3 years
• •20. Female patients of child-bearing potential who are not using adequate birth control methods, or who are pregnant or breast feeding.
• •21. Patients who are using other investigational agents or who had received investigational drugs ≤ 2 weeks prior to study treatment start.
• •22. Patients unwilling or unable to comply with the protocol.