Efficacy and Safety Comparison of RAD001 Versus Sunitinib in the First-line and Second-line Treatment of Patients With Metastatic Renal Cell Carcinoma (RECORD-3)

Inclusion Criteria:

1. Patients with advanced renal cell carcinoma.
2. Patients with at least one measurable lesion.
3. Patients with a Karnofsky Performance Status ≥70%.
4. Adequate bone marrow function.
5. Adequate liver function.
6. Adequate renal function.
7. Left ventricular ejection fraction (LVEF) ≥ lower limit of institutional normal (LLN)
8. 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:

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. Untreated 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 ≥150mmHg or diastolic blood pressure (DBP) of ≥ 90mmHg]
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 02 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.

Other protocol-defined inclusion/exclusion criteria may apply