Everolimus Versus Sunitinib in Non-Clear Cell Renal Cell Carcinoma

Inclusion Criteria: 1. Patients must have advanced non-clear cell RCC, which may include but is not limited to the following subtypes: papillary I or II, chromophobe, collecting duct carcinoma (CDC), translocation or unclassified. Patients with conventional-type renal cell carcinoma who have \>/= 20% sarcomatoid component in their primary tumor are eligible. Patients who have sarcomatoid features in FNA or core biopsy of any metastatic site are eligible, if they have an underlying renal cell carcinoma primary tumor. 2. Patients must have at least one measurable site of disease that has not been previously irradiated. If the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation 3. ECOG performance status 0-1 4. Age \>/= 18 years 5. Patients must have adequate organ and marrow function within 14 days prior to study entry as defined below: a) Hemoglobin \>/= 9 g/dl (tx allowed); b) absolute neutrophil count \>/=1,500/microL; c) platelets \>/= 100,000/microL; d) total bilirubin \</= 1.5 mg/dl; e) AST(SGOT) or ALT (SGPT) \</=2.5 X institutional uln, except in known hepatic metastasis, wherein may be \</= 5 x ULN; f) Serum Creatinine \</= 1.5 x ULN (as long as patient does not require dialysis) 6. INR and PTT \</= 1.5 x ULN within 14 days prior to study entry. Therapeutic anticoagulation with warfarin is allowed if target INR \</= 3 on a stable dose of warfarin or on a stable dose of LMW heparin for \> 2 weeks (14 days) at time of randomization. 7. Fasting serum cholesterol \</= 300 mg/dL OR \</= 7.75 mmol/L AND fasting triglycerides \</= 2.5 x ULN within 14 days prior to study entry. 8. Female patients of childbearing potential (not postmenopausal for at least 12 months and not surgically sterile) must have a negative serum or urine pregnancy test within 14 days before study entry. Pregnancy test must be repeated if performed \> 14 days before starting study drug. 9. Patients must give written informed consent prior to study entry, in keeping with the policies of each institution. 10. Patients with a history of major psychiatric illness must be judged (by the treating physician) able to fully understand the investigational nature of the study and the risks associated with the therapy. 11. Patients with controlled brain metastases are allowed on protocol if they had solitary brain metastases that was surgically resected or treated with radiosurgery or Gamma knife, without recurrence or edema for 3 months (90days). Exclusion Criteria: 1. No other malignancies within the past 2 years except for adequately treated carcinoma of the cervix or basal (without recurrence post-surgery or post-radiotherapy) or squamous cell carcinomas of the skin. 2. No prior systemic therapy for RCC including prior adjuvant therapy or investigational drug is allowed. 3. Patients currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks (28 days) from enrollment into this study (including chemotherapy and targeted therapy) are excluded. However, patients are permitted to receive bisphosphonates. Also, patients who completed palliative radiation therapy prior to enrollment in this trial are eligible. 4. Patients, who have had a major surgery or significant traumatic injury (injury requiring \> 4 weeks (28 days) to heal) within 4 weeks (28 days) of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patients that may require major surgery during the course of the study. 5. Concomitant treatment with rifampin, St. John's wort, or the cytochrome p450 enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine or Phenobarbital) or CYP3A4 inhibitors is not recommended on this study. 6. Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as: a) Symptomatic congestive heart failure of New York heart Association Class III or IV; b) unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease; c) severely impaired lung function as defined as 02 saturation that is 88% or less at rest on room air 7. (#6 cont'd) d) uncontrolled diabetes as defined by fasting serum glucose \>1.5 x ULN; e) active (acute or chronic) or uncontrolled severe infections requiring antibiotic intervention; f) liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis 8. Patients must not have history of other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of sunitinib or everolimus or that might affect the interpretation of the results of the study or render the subject at high risk from treatment complications. 9. Concomitant treatment with drugs with dysrhythmic potential (terfenadine, quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, and indapamide) is not recommended. 10. Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent. Topical or inhaled corticosteroids are allowed. 11. Patients should not receive immunization with attenuated live vaccines within one week (7 days) of study entry or during study period. 12. Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases. 13. A known history of HIV sero-positivity. 14. Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of everolimus and/or sunitinib (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection). 15. Patients with an active, bleeding diathesis. 16. Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. If barrier contraceptives are being used, these must be continued throughout the trial by both sexes. Hormonal contraceptives are not acceptable as a sole method of contraception. (Women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to study entry. Pregnancy test must be repeated if performed \> 7 days before administration of everolimus and sunitinib)