Phase III Sequential Open-label Study to Evaluate the Efficacy and Safety of Sorafenib Followed by Pazopanib Versus Pazopanib Followed by Sorafenib in the Treatment of Advanced / Metastatic Renal Cell Carcinoma (SWITCH-II)

Inclusion Criteria: 1. Patients with metastatic / advanced RCC (all histologies), who are not suitable for cytokine therapy and for whom study medication constitutes first-line treatment. For cytokine- unsuitability at least one of the following criteria must be fulfilled\*: * Age 66 to 88 years * Non-clear cell histology RCC * Intermediate risk according to MSKCC score * ECOG ≥ 1 and\> 1 organ metastasis + \< 24 months between diagnosis and establishing indication for interleukin-2-therapy * ECOG ≥ 1 and "unable to carry on normal activity or do active work" (Karnofsky Index 70%) * Creatinine ≥ 1x ULN and \< 2x ULN * Total bilirubin ≥ 1x ULN and \< 1.5x ULN * Present autoimmune disease * Patients who might require steroids * Hypersensitivity against cytokines * Severe organic disease, not interfering with other in-/exclusion criteria of the Switch-2 study * Non-symptomatic brain metastases * Severe lung disease (e.g. PAH, COPD) with Pa O2 \< 60 mmHg on rest 2. Age ≥ 18 and ≤ 85 years 3. Karnofsky Index ≥ 70% (see appendix 15.1) 4. MSKCC prognostic score (2004), low or intermediate (see appendix 15.2) 5. Life expectancy of at least 12 weeks 6. Subjects with at least one uni-dimensional (for RECIST 1.1) measurable lesion. Lesions must be measured by CT/MRI- scan 7. Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to start of therapy: * hemoglobin \> 9.0 g/dl * absolute neutrophil count (ANC) \> 1,500 µl * Platelet count ≥ 100,000 / µl * total bilirubin \< 1.5x the upper limit of normal (Note: Subjects with Gilbert' Syndrome are eligible if their total bilirubin is \< 3.0 X ULN and direct bilirubin ≤ 35 %). * ALAT and ASAT \< 2.5x upper limit of normal (Note: concomitant elevations in bilirubin ans ASAT/ALAT above 1.0x upper limit of normal are not permitted). * Alkaline phosphatase \< 4x upper limit of normal * PT-INR/aPTT \< 1.2x upper limit of normal (Patients who are being therapeutically anticoagulated with an agent such as coumadin or heparin will be allowed to participate provided that their INR is stable and within the recommended range for the desired level of anticoagulation and no prior evidence of underlying abnormality in these parameters exists). * Serum creatinine \< 2x upper limit of normal 8. Written Informed Consent Exclusion Criteria: 1. History of cardiac disease: congestive heart failure \> NYHA class 2 or with LVEF at baseline echocardiography \< 50%, (echocardiography is optional); active CAD (MI more than 6 months prior to study entry is allowed); cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted) 2. Uncontrolled hypertension (defined as blood pressure ≥ 150 mmHg systolic and/or ≥ 90 mmHg diastolic on medication). 3. History of HIV infection or chronic hepatitis B or C 4. 4\. Active clinically serious infections (\> grade 2 NCI-CTC version 4.03) 5. Symptomatic metastatic brain or meningeal tumors (unless the patient is \> 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry) 6. Patients with seizure disorder requiring medication (such as steroids or anti-epileptics) 7. Patients with evidence or history of bleeding diathesis 8. History of organ allograft 9. Major surgery within 4 weeks of start of study 10. Autologous bone marrow transplant or stem cell rescue within 4 months before study start. 11. Any significant condition that increases the risk for bleeding, including, but not limited to active peptic ulcer disease, inflammatory bowel disease, known intraluminal or endobronchial metastatic lesions and/or lesions infiltrating major pulmonary vessels with risk of bleeding, presence of non-healing wound or trauma within 4 weeks prior to first dose of investigational drug 12. History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep vein 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) 13. Corrected QT Interval (QTc) \> 480 msecs 14. Untreated hypothyroidism 15. Patients undergoing renal dialysis 16. Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors \[Ta, Tis \& T1\] or any cancer curatively treated \> 3 years prior to study entry 17. Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Both men and women enrolled in this trial must use adequate barrier birth control measures (with a Pearl Index \< 1) during the course of the trial and 3 months after the completion of trial 18. Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results 19. Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study 20. Patients unable to swallow oral medications 21. Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product 22. Known allergy to Votrient or Nexavar (i.e. to active substance or one of the constituents) 23. Prior exposure to study drugs. 24. Investigational drug therapy within 4 weeks of study entry. 25. Use of biologic response modifiers, such as G-CSF and other hematopoietic growth factors, within 3 weeks of study entry 26. Radiotherapy within 3 weeks of start of study drug and planned radiotherapy during the study 27. Concomitant medication: Any condition at the discretion of the investigator that precludes compliance with concomitant therapy restrictions described below.