Inclusion Criteria:

- Signed Informed Consent

- Documented progressive disease prior to study inclusion.

- Adult males and females: ≥ 18 years of age.

- Metastatic or locally advanced RCC, not amendable to surgery with curative intention.

- ECOG performance status 0-1.

- Patients with measurable disease (at least one uni-dimensionally measurable target
lesion by CT-scan or MRI) according to Response Evaluation Criteria in Solid Tumors
(RECIST 1.1) If prior palliative radiotherapy to metastatic lesions: ≥ 1 measurable
lesion that has not been irradiated. Patients with bone lesions as the only
measurable lesion are eligible, provided that lesions consist of soft tissue, which
is assessed via CT or MRI.

- Prior radiotherapy and surgery are allowed if completed 4 weeks (for minor surgery 2
weeks) prior to start of treatment and patient recovered from toxic effects.

- Modified MSKCC risk (according to Heng): good or intermediate.

- White blood cell count (WBC) ≥ 4x10*9/L with neutrophils ≥ 1.5 x 10*9/L, platelet
count ≥ 100x10*9/L, hemoglobin ≥ 9 g/dL.

- Total bilirubin ≤ 2 x upper limit of normal.

- AST and ALT ≤ 2.5 x upper limit of normal, or ≤ 5 x upper limit of normal in case of
liver metastases.

- Serum creatinine ≤ 2 x upper limit of normal or calculated creatinine clearance >30
ml/min.

- International Normalized Ratio (INR) ≤1.5 except for patients on stable anticoagulant
therapy. Activated partial thromboplastin time (aPTT) ≤1.5 times upper limit of
normal (ULN) or greater than the lower limit of the therapeutic range. Note: The use
of full-dose oral or parenteral anticoagulants is permitted as long as the INR or
aPTT is within therapeutic limits (according to the medical standard in the
institution) and the patient has been on a stable dose of anticoagulants for at least
two weeks at the treatment start.

- Adequate cardiac function (left ventricular ejection fraction ≥50% as assessed by
ECHO)

Exclusion Criteria:

- Any investigational drug within the 30 days before inclusion.

- Known or suspected allergy or hypersensitivity reaction to any of the components of
study treatments or their excipients.

- Pregnancy (absence to be confirmed by beta-hCG test) or lactation period.

- Men or women of child-bearing potential who are sexually active and unwilling to use
a highly effective method of contraception (Pearl index < 1%) during the trial. Oral
contraceptives are acceptable if a barrier method is applied in conjunction.

- Clinically symptomatic brain or meningeal metastasis (known or suspected), unless
completion of local therapy for at least 3 months with discontinuation of steroids
prior to start of treatment.

- Cardiac arrhythmias requiring anti-arrhythmics (excluding beta blockers, digoxin or
digitoxin).

- History of any of the following cardiac events within the past 6 months:

1. myocardial infarction (including severe/unstable angina),

2. coronary/peripheral artery bypass graft,

3. congestive heart failure (CHF) (NYHA Class III, or IV),

4. cerebrovascular accident,

5. transient ischemic attack,

6. pulmonary embolism, abdominal or tracheo-oesophageal fistula, gastrointestinal
perforation, or intra-abdominal abscess

- Hemorrhage ≥ grade 3 or clinically significant hemoptysis within the past 4 weeks

- Uncontrolled severe hypertension (failure of diastolic blood pressure to fall below
90 mm Hg despite the use of ≥ 3 anti-hypertensive drugs).

- History of relevant pulmonary hypertension or interstitial lung disease or severely
impaired lung function.

- Acute or sub-acute intestinal occlusion or history of inflammatory bowel disease or
chronic diarrhea.

- Previous malignancy (other than renal cell cancer) in the last 3 years, except basal
cell cancer of the skin, pre-invasive cancer of the cervix, T1a prostate carcinoma or
superficial bladder tumor [Ta, Tis and T1].

- History of organ allograft.

- Significant disease which, in the investigator's opinion would exclude the patient
from the study.

- Medication that is known to interfere with any of the agents applied in the trial.

- Patients with a serious non-healing wound, ulcer or bone fracture.

- Patients with a history of seizure(s) not controlled with standard medical therapy.

- Patients receiving chronic systemic treatment with corticosteroids (dose of > 20
mg/day methylprednisone equivalent) or another immune-suppressive agent. Inhaled and
topical steroids are acceptable.

- Legal incapacity or limited legal capacity.

- Medical or psychological conditions that would not permit the patient to complete the
study or sign informed consent.

- Significant vascular disease (e.g. aortic aneurysm, aortic dissection), or
symptomatic peripheral vascular disease.

- Evidence or history of recurrent thromboembolism (>1 episode of deep venous
thrombosis/peripheral embolism ≥ CTCAE Grade 3) during the past 2 years, bleeding
diathesis or coagulopathy.

- Poorly controlled diabetes as defined by fasting serum glucose > 2.0 x ULN.

- Active (acute or chronic) or uncontrolled infection of bacterial, mycotic or viral
genesis.

- Liver disease such as chronic active hepatitis or chronic persistent hepatitis.

- Patients with a known history of HIV seropositivity.

- QT prolongation (QTc > 450 msec).