Study of Interleukin-2, Interferon-alpha and Bevacizumab in Metastatic Kidney Cancer

Inclusion Criteria: 1. Signed written informed consent 2. Patient must be willing and able to comply with the protocol. 3. Age ≥ 18 years. 4. Histologic og cytologic biopsy proven locally advanced or metastatic renal cell carcinoma, considered non-candidates for curative surgery. Nephrectomy is not mandatory. 5. Patient with renal cell carcinoma (RCC) with a clear-cell histologic component confirmed by local pathology review. 6. Females with a negative serum pregnancy test unless childbearing potential can be otherwise excluded 7. Fertile women of childbearing potential (\<2 years after last menstruation) and men must use effective means of contraception 8. Memorial-Sloan-Kettering-Cancer-Centre favourable- and intermediate prognostic group. 9. Measurable or non-measurable disease (as per RECIST1.1 criteria) 10. Karnofsky Performance status of 70% or higher. 11. Life expectancy greater than 4 months. 12. The required laboratory values at baseline are as follows: Haematology: WCC ≥ 3.0 x 109/L, Platelet count ≥ 100 x 109/L, Haemoglobin ≥ 6.2 mmol/l, (INR) ≤ 1.5, APTT ≤ 1.5 x ULN Biochemistry: Total bilirubin ≤ 1.5 x upper limit of normal (ULN), AST, ALT ≤ 2.5 x ULN in patients without liver metastases, ≤ 5 x ULN in patients with liver metastases, Serum Creatinine ≤ 150 micromol/L \- Exclusion Criteria: 1. Prior systemic treatment for metastatic RCC disease 2. Major surgical procedure, open surgical biopsy, or significant traumatic injury within 28 days prior to randomization. 3. Serious non-healing wound, ulcer or bone fracture. 4. Evidence of current central nervous system (CNS) metastases or spinal cord compression. Patient must undergo an MRI or CT scan of the brain (with contrast, if possible) within 28 days prior to randomization. 5. Seizure(s) not controlled with standard medical therapy. 6. Dipstick urine test of protein ≥ 2+. 7. Other malignancies within 5 years prior to randomization (other than curatively treated basal cell carcinoma of the skin and/or in situ carcinoma of the cervix). 8. Evidence of bleeding diathesis or coagulopathy. 9. Ongoing or recent (within 10 days prior to study treatment start) need for full therapeutic dose of oral anticoagulants or chronic daily treatment with aspirin. Low molecular weight heparin are allowed 10. Uncontrolled hypertension (≥ 160 mm Hg systolic and/or ≥ 100 mm Hg diastolic) while receiving chronic medication. 11. Clinically significant (i.e. active) cardiovascular disease, for example cerebrovascular accidents (≤ 6 months before randomisation), myocardial infarction (≤ 6 months before randomisation), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, or serious cardiac arrhythmia requiring medication. 12. Recent (within the 30 days prior to randomization) treatment with another investigational drug or participation in another investigational study. 13. Chronic treatment with corticosteroids (dose of ≥ 10 mg/day methylprednisolone equivalent), excluding inhaled steroids. 14. History or presence of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or patient at high risk from treatment complications. 15. Known hypersensitivity to interleukin-2, Interferon, alfa or bevacizumab. Serial blood test, serial tumor biopsies and serial dynamic contrast-enhanced imaging will be obtained as part of a translational research program integrated in the clinical trial. Part(s) of the translational research program may be omitted in the individual patient due to practical, technical or safety reasons, without having consequences for participating in the additional translational research investigations or the clinical part of the study. \-