Efficacy Study of Sunitinib and Everolimus (Rotational vs Sequential Arm) in Pats. With m Clear Cell Renal Cancer

Inclusion Criteria:

* Renal cell carcinoma with a predominant clear cell component confirmed by histology.
* Advanced disease: metastatic AND, not suitable for resection
* Male or female, aged 18 years or older
* ECOG (Eastern Cooperative Oncology Group) Performance Status of 0 or 1
* Low or intermediate MSKCC (Memorial Sloan Kettering Cancer Center) prognostic risk score,i.e. no more than 2 of the following:

  * Karnofsky performance status (\<80%)
  * Low serum hemoglobin (≤ 13 g/dL for males and ≤ 11.5 g/dL for females)
  * High corrected serum calcium (≥ 10 mg/dL)
* Target and/or non-target lesions according to RECIST 1.1 ( Response Evaluation Criteria in Solid Tumors)
* Expected survival of at least 3 months.
* No prior systemic treatment. But adjuvant treatment is ok if stopped from ≥ 24 months
* Adequate bone marrow function as shown by:
* Adequate liver function as shown by:
* Adequate renal function as shown by serum creatinine ≤ 1.5 x ULN (upper limit of normal)
* Left ventricular ejection fraction ≥55% on gated cardiac blood pool scan, or normal left ventricular function and fractional shortening on echocardiogram (according to institutional limits).
* SBP (systolic blood pressure) ≤140mmHg and DBP (diastolic blood pressure)

  * 90mmHg (it is acceptable to initiate antihypertensive treatment prior to registration to achieve these goals).
* Able to commence treatment within 7 days of registration.
* Willing and able to comply with follow-up and all other protocol requirements.
* Written informed consent

Exclusion Criteria:

* Prior treatment with VEGF-targeting agents or multi-kinase inhibitors or mTOR-targeting agents
* Active central nervous system metastases.
* Other malignancy diagnosed within the last 5 years, except the following if adequately treated: superficial squamous cell carcinoma or basal cell carcinoma of skin, superficial bladder cancer (T1 and G1 or T1 and G2), stage 1 cervical cancer.
* Treatment with an investigational agent in the last 4 w.
* Known to be HIV positive.
* Evidence of chronic hepatitis due to hepatitis B virus (HBV) or hepatitis C virus (HCV)
* Clinically significant heart disease (NYHA Class III or IV)
* History of hypertension requiring hospitalization.
* Other serious illnesses,
* Immunotherapy or chemotherapy in the last 4 w (6 weeks for nitrosoureas)
* Major surgery in the last 4 w, or planned in the next 6 w
* Radiation therapy in the last 2 w, or planned in the next 6 w
* NCI CTCAE (Common Toxicity Criteria for Adverse Effects) version 4.0 grade 3 or worse hemorrhage in last 4 w.
* Any of the following in the last year: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism.
* Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication.
* Ongoing cardiac dysrhythmias of NCI CTCAE version 4.0 grade ≥2, atrial fibrillation of any grade, or prolongation of the corrected QT interval (QTc) to \>450 msec for males or \>470 msec for females
* Uncontrolled diabetes as defined by fasting serum glucose \>1.5 X ULN.
* Pregnancy,lactation. Inadequate contraception.
* Known allergy or hypersensitivity to everolimus, sunitinib or iodine.
* Medical or psychiatric condition that compromises the patient's ability to give informed consent.