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

Inclusion Criteria

• Patients with advanced renal cell carcinoma.
• Patients with at least one measurable lesion.
• Patients with a Karnofsky Performance Status ≥70%.
• Adequate bone marrow function.
• Adequate liver function.
• Adequate renal function.
• Left ventricular ejection fraction (LVEF) ≥ lower limit of institutional normal (LLN)
• Women of childbearing potential must have had a negative serum pregnancy test within 14 days prior to the administration of the study medication. Adequate contraception must be used while on study.

Exclusion Criteria

• Less than 4 weeks post-major surgery
• 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).
• Patients in need for major surgical procedure during the course of the study
• Patients with a serious non-healing wound, ulcer, or bone fracture
• Patients with a history of seizure(s) not controlled with standard medical therapy
• Patients who have received prior systemic treatment for their metastatic RCC
• 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.
• 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
• Patients with a known hypersensitivity to sunitinib or its excipients
• 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)
• 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.
• Poorly controlled hypertension [defined as systolic blood pressure (SBP) of ≥160mmHg or diastolic blood pressure (DBP) of ≥ 95mmHg]
• Patients receiving chronic systemic treatment with corticosteroids or another immunosuppressive agent
• Patients with a known history of HIV seropositivity.
• Patients with active bleeding.
• 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