Combined Alternating Sunitinib and Bevacizumab (Avastin®) in Advanced Renal Cell Carcinoma (CASA)

Inclusion Criteria: 1. Histologically confirmed renal cell carcinoma with clear cell histology ( mixed histology with clear cell component is accepted) 2. Patient should have either locally advanced or metastatic disease 3. No prior anti-cancer therapy 4. Age ≥ 18 years 5. Life expectancy of 3 months or more 6. Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1 7. Performance status 0-2 by ECOG scale 8. Patients with controlled brain metastasis are accepted 9. Adequate renal function: serum creatinine ≤ 2 times the institutional upper limit of normal 10. Adequate hepatic function: total bilirubin within normal institutional limits, serum AST and ALT levels ≤2 times the institutional upper limit of normal or ≤ 5 times the institutional upper limit of normal of elevated because of liver involvement 11. Coagulation (PT ≤ 1.5 times the institutional upper limit of normal) 12. Adequate hematological values: leukocyte count ≥3.0 x 109/L, an absolute neutrophil count ≥1.5 x 109/L, a platelet count ≥100 x 109/L and hemoglobin ≥ 9.0 g/dL 13. Urine dipstick for proteinuria \<1+, patients discovered to have ≥ 1+ on dipstick urinanalysis at baseline should have urine protein/urine creatinine ratio ≤1 14. Singed written informed consent before enrolment 15. Patient should have unresectable disease ( for both the primary tumor and the metastasis) Exclusion Criteria: 1. Inability to comply with the protocol therapy 2. Uncontrolled hypertension defined as BP more than 160 systolic and or more than 100 diastolic despite adequate treatment at the time of treatment initiation. 3. Severe cardiovascular disease (congestive heart failure NYHA III or IV, unstable angina pectoris, myocardial infarction, significant arrhythmias or Transient ischemic attack (TIA) or cerebrovascular accident (CVA) in the last 6 months 4. Major bleeding disorder, significant traumatic injury or recent major surgery within 28 days of starting therapy. Or minor surgery (FNA/Core biopsy) within 7 days of starting therapy 5. History of abdominal abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months 6. Pre-existing thyroid abnormality 7. Concurrent proarrhythmic medications including terfenadine, quinidine, procainamide, disopyramide, sotalol, bepridil, haloperidol, risperidone, indapamide and flecainide 8. Recent significant hemoptysis (1/2 tea spoon red blood within last month) 9. Concurrent medication that either CYP 450 3A4 inducers or inhibitors 10. Concurrent use of proarrhythmic medications including terfenadine, quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, indapamide and flecainide 11. Pregnancy or breast feeding, or patient refusal to use appropriate contraception for female patients in childbirth age 12. Previous malignancy within 5 years, except adequately treated non melanomatous skin cancer or in situ cervical cancer 13. Psychiatric or mental disorder, precluding understanding of the information of the trial related topics and giving valid informed consent 14. Any psychological, familial, geographic or social circumstances which could impair the patient ability to participate in the trial and comply with follow up. 15. Any circumstance which might impair the patient's ability to comply with an out-patient regimen 16. Active uncontrolled infection 17. Serious underlying medical condition (in the judgment of the investigator) which could impair the ability of the patient to participate in the trial 18. Treatment with other experimental drugs within 30 days of entry into the trial 19. Treatment with other anti-cancer therapy 20. Legal incapacity 21. Significant proteinuria (urine protein: creatinine ratio \> 1.0)