Safety and Efficacy of Bevacizumab Plus RAD001 Versus Interferon Alfa-2a and Bevacizumab in Adult Patients With Kidney Cancer (L2201)

• Overall survival (OS) treatment effect in patients who receive RAD001 plus bevacizumab versus patients who receive IFN plus bevacizumab [ Time Frame: 2 years after the last patient randomized in the study ] [ Designated as safety issue: No ]
• Objective response rate and response duration differences in patients who receive RAD001 plus bevacizumab versus patients who receive IFN plus bevacizumab [ Time Frame: when a total of 200 PFS events have been observed ] [ Designated as safety issue: No ]
  per independent central radiological review
• Safety profile of RAD001 plus bevacizumab versus IFN plus bevacizumab [ Time Frame: until the last patient discontinued the study treatment + 28 days ] [ Designated as safety issue: Yes ]
• Quality of life (QoL) of patients treated with RAD001 plus bevacizumab versus patients treated with IFN plus bevacizumab. [ Time Frame: when a total of 200 PFS events have been observed ] [ Designated as safety issue: No ]
  the timeframe is based on by the central review, however the actual QoL data is in the clinical database
• Exposure of RAD001 in patients randomized to the treatment combination of RAD001 and bevacizumab [ Time Frame: until the last patient discontinued the study treatment + 28 days ] [ Designated as safety issue: No ]

To estimate the difference in efficacy and safety of bevacizumab and RAD001 compared to bevacizumab and interferon alfa-2a for first-line treatment of patients with metastatic carcinoma of the kidney.

• Carcinoma, Renal Cell
• Adenocarcinoma, Renal Cell
• Nephroid Carcinoma
• Carcinoma, Hypernephroid

• Drug: bevacizumab, RAD001(Everolimus)
  Other Name: Afinitor
• Drug: bevacizumab, interferon alfa-2a

• Experimental: bevacizumab, RAD001
  Intervention: Drug: bevacizumab, RAD001(Everolimus)
• Active Comparator: bevacizumab, interferon alfa-2a
  bevacizumab plus RAD001(Everolimus) versus bevacizumab and interferon alfa-2a
  Intervention: Drug: bevacizumab, interferon alfa-2a

Inclusion Criteria:

1. Patients with metastatic renal cell carcinoma
2. Patients with at least one measurable lesion
3. Patients with progressive metastatic renal cell carcinoma
4. Patients who had a prior partial or complete nephrectomy
5. Patients with a Karnofsky Performance Status ≥70%.
6. Adequate bone marrow function
7. Adequate liver function
8. Adequate renal function
9. Adequate coagulation profile

Exclusion Criteria:

1. 4 weeks post-major surgery
2. Patients who had radiation therapy within 28 days prior to start of study
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 received prior therapy with VEGF pathway inhibitor
8. Patients who have previously received systemic mTOR inhibitors
9. Patients with a known hypersensitivity RAD001 (everolimus) or other rapamycins or to its excipients.
10. Patients with history or current central nervous system (CNS) metastases or spinal cord compression.
11. Patients with a history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment.
12. Patients with proteinuria at screening.
13. Patients with inadequately controlled hypertension
14. Patients receiving ongoing or with recent need for full therapeutic dose of oral or parenteral anticoagulants or chronic daily treatment with aspirin
15. Patients receiving chronic systemic treatment with corticosteroids or another immunosuppressive agent.
16. Patients with a known history of HIV
17. Patients with hypersensitivity to interferon alfa-2a or any component of the product.
18. Patients with an active, bleeding diathesis or coagulopathy or recurrent thromboembolism
19. Patients who have any severe and/or uncontrolled medical conditions or other conditions
20. Left Ventricular Ejection Fraction < lower limit of institutional normal assessed by ECHO or MUGA
21. Patients who have a history of another primary malignancy ≤ 3 years
22. Female patients who are pregnant or breast feeding
23. Patients who are using other investigational agents or who had received investigational drugs ≤ 4 weeks prior to study treatment start.
24. Patients unwilling to or unable to comply with the protocol

Other protocol-defined inclusion/exclusion criteria may apply