Inclusion Criteria:

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

2. Locally advanced or metastatic, histological confirmed, non-clear cell RCC of all
subtypes. Patients must have advanced non-clear cell of one of the following
subtypes: papillary, chromophobe, collecting duct carcinoma (CDC), renal medullary
carcinoma (RMC), or unclassified.

3. 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.

4. PS 0-2 ECOG

5. Signed written informed consent.

6. 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.]

7. Total bilirubin <2 x upper limit of normal.

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

9. Serum creatinine <2.0 x upper limit of normal.

10. Normal ECG without QT prolongation (QTc < 450msec).

11. Adequate cardiac function (left ventricular ejection fraction > 40% as assessed by
ECHO.

Exclusion Criteria:

1. Predominant clear-cell RCC

2. Resectability or other curative options

3. Any investigational drug within the 30 days before inclusion.

4. Prior systemic treatment for their RCC.

5. Known or suspected allergy or hypersensitivity reaction to any of the components of
study treatments.

6. Radiotherapy within the last 4 weeks.

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

8. Men or women of child-bearing potential who are sexually active and unwilling to use
a medically acceptable method of contraception during the trial.

9. Clinically symptomatic brain or meningeal metastasis. (known or suspected)

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

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

- myocardial infarction (including severe/unstable angina),

- coronary/peripheral artery bypass graft,

- congestive heart failure (CHF),

- cerebrovascular accident,

- transient ischemic attack,

- pulmonary embolism.

12. No hemorrhage ≥ grade 3 within the past 4 weeks

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

14. History of relevant pulmonary hypertension or interstitial lung disease.

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

16. Previous malignancy (other than renal cancer cancer) in the last 5 years except basal
cell cancer of the skin, pre-invasive cancer of the cervix or superficial bladder
tumor [Ta, Tis and T1].

17. History of organ allograft

18. Significant disease which, in the investigator`s opinion would exclude the patient
from the study

19. Patients with seizure and epileptic disorder or other conditions requiring medication
(such as phenytoin, carbamazepin, phenobarbital)

20. Patients under strong inducers or inhibitors to CYP Isoenzymes

21. Patients with hypersensitivity to the antihistamine or patients who cannot receive
the antihistamine for other medical reasons

22. Patients requiring long-term cortisone therapy

23. Patients requiring oral anticoagulation treatment, such as marcoumar.
(Anticoagulation treatment with heparin or low molecular weight heparin [LMWH] is
allowed provided that close monitoring is performed).

24. Surgery within at least 2 weeks prior to randomization

25. HIV seropositivity.

26. Abnormal pulmonary function (DLCO < 50%). [Pulmonary function tests need only to be
performed if abnormal pulmonary function present in medical history].

27. Poorly controlled diabetes mellitus.

28. Liver cirrhosis, chronic hepatitis

29. Legal incapacity or limited legal capacity

30. Known alcohol or drug abuse.

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