Safety and Efficacy of Bevacizumab Plus RAD001 Versus Interferon Alfa-2a and Bevacizumab for the First-line Treatment in Adult Patients With Kidney Cancer
Condition: Carcinoma; Adenocarcinoma; Renal Cell; Nephroid Carcinoma; Hypernephroid
MeSH terms: Carcinoma; Carcinoma, Renal Cell
Intervention: RAD001(everolimus); interferon alfa-2a; bevacizumab
Intervention description: 10 mg qd; dose escalated from 3 MIU (million international unit) during week 1, 6 MIU during week 2, and 9 MIU during week 3; 10 mg/kg every 2 weeks
Intervention MeSH terms: Interferons; Interferon-alpha; Interferon alpha-2; Bevacizumab; Everolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 365.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Renal cell carcinoma; Adults; Bevacizumab; RAD001; Everolimus; Interferon; Clear; Roferon; Avastin; Nephrectomy; newly diagnosed

Summary:

      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.
    

Eligibility criteria:

        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