**ACRIN Approval Needed for DCE-MRI Sub-Study** SJMH-Ann Arbor is the only Sites CCOP Wide ACRIN Approved**

1. Patients will be required to have the clear cell variant of renal cell carcinoma with less than 25% of any other histology (including, but not limited to, papillary or chromophobe or oncocytic). There must be histologic confirmation by treating center of either primary or metastatic lesion.

2. Patients will be required to have measurable metastatic disease (as defined in Section 6.1.1) that is not curable by standard radiation therapy or surgery. All sites must be assessed within 4 weeks prior to study entry.

3. Previous nephrectomy is required with the following exceptions:

a. primary tumor < 5cm, or

b. extensive liver (> 30% of liver parenchymal) or multiple (> 5) bone metastases, making nephrectomy a clinically questionable procedure.

4. Patients will be allowed no more than one prior regimen containing a vaccine or cytokine based immunotherapy for advanced disease.

5. No prior anti-angiogenic therapy including, but not limited to, SU11248, ZD6474 or VEGF Trap. No prior therapy with bevacizumab, mTOR inhibitors (including, but not limited to, temsirolimus), or sorafenib will be allowed. Thalidomide or IFNá are allowed either for adjuvant therapy or stage IV disease.

6. No immunotherapy within 4 weeks of randomization. Toxicities from immunotherapy must have resolved and a minimum of two weeks must pass prior to enrollment.

7. Prior radiation therapy is permitted, but toxicities from radiation must have resolved and a minimum of 2 weeks must pass prior to randomization.

8. No history or clinical evidence of CNS disease, including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastasis, or history of stroke within the past 48 weeks.

9. Age > 18 years of age.

10. ECOG performance status of 0 or 1 (see Appendix XII).

11. Life expectancy of greater than 12 weeks.

12. Patients will have the following baseline laboratory values within 2 weeks prior to randomization:

Hgb> 9.0gm/dL (transfusions allowed prior to enrollment)

White Blood Count (WBC) > 3,000/mm3

Absolute Granulocyte Count (AGC) > 1,200/mm3

Platelet Count > 100,000/mm3

Serum creatinine < 1.5 X upper limit of normal (ULN)

or serum creatinine clearance (CrCl) > 55 ml/min

Total Bilirubin < 1.5 x ULN

AST and ALT < 2.5 x ULN (or < 5.0 x ULN in the presence of liver metastases)

INR < 1.5 and aPTT within normal limits

Fasting Cholesterol < 350 mg/dL (9.0 mmol/L)

Fasting Triglycerides < 400 mg/dL (4.56 mmol/L)

13. Patients must not have other current malignancies, other than basal cell skin cancer, squamous cell skin cancer, in situ cervical cancer, and ductal or lobular carcinoma in situ of the breast. Patients with other malignancies are eligible if they have been continuously disease-free for > 5 years prior to the time of randomization.

14. No history of allergic reactions attributed to Chinese hamster ovary cell products, other recombinant human antibodies, or compounds of similar chemical or biologic composition to sorafenib, temsirolimus or bevacizumab.

15. No history of bleeding diathesis or coagulopathy.

16. Any condition that impairs patient?s ability to swallow pills will make patient ineligible.

17. No major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to randomization.

18. No anticipated need for major surgery during the course of the study.

19. No current or recent (within 4 weeks of enrollment) use of full-dose of anticoagulants or thrombolytic agents (except as required to maintain patency of preexisting or permanent indwelling IV catheters, for those patients receiving warfarin, INR must be < 1.5).

20. No clinically significant cardiovascular disease, defined as one of the following:

? Patients with uncontrolled hypertension (blood pressure > 150/100 mm/Hg at the time of enrollment). Patients with hypertension and blood pressure < 150/100 mm/Hg on stable antihyperte

1. Patient must have histologically confirmed metastatic or unresectable renal cell carcinoma. Patient must have a component of conventional clear cell renal carcinoma. Patients with true papillary, sarcomatoid features without any clear cell component, chromophobe, oncocytoma, collecting duct tumors and transitional cell carcinoma are NOT eligible.

2. Patient must have measurable lesions according to the RECIST criteria (per Section 6.0). Baseline measurements must be performed within 4 weeks prior to randomization.

3. Patient must have evidence of progressive disease following treatment with a tyrosine kinase inhibitor as assessed by the site investigator on the basis of CT scans and other appropriate clinical documentation.

4. Patient must have received one (and only one) prior treatment with either Sutent or Nexavar for at least 12 weeks. Prior immunotherapy (interleukin 2 and interferon alpha only) is allowed. Treatment with TKI must have ended = 1 week prior to starting treatment with AVE0005 (VEGF Trap) and all toxicities must have resolved.

5. No prior chemotherapy, cellular therapy, vaccine therapy or hormonal therapy is allowed.

6. Previous RT is permissible provided the measurable disease is outside the RT port. RT must be completed > 3 weeks prior to randomization.

7. Patient must be 18 years of age or older.

8. Patient must have an ECOG performance status 0-2.

9. Patient must have recovered from any toxic effects of prior radiotherapy or surgical procedures.

10. Patient must have adequate organ function as defined by the following criteria (within 4 weeks prior to study entry):

? SGOT (AST) and SGPT (ALT) <=3 x ULN

? Total serum bilirubin <=1.5 x ULN

? Absolute neutrophil count (ANC) >=1 x 109/L

? Platelet count >=100 x 109/L

? Hemoglobin >=8.0 g/dL

? Serum calcium <=12.0 mg/dL

? Calculated creatinine clearance (CrCl) =60 mL/min, and either proteinuria <=500 mg/24 hours or urine protein:creatinine ratio (UPCR) <=1

? International normalized ratio (INR) within normal limits (or <=1.5 x ULN if on prophylactic anticoagulation) and activated partial thromboplastin time (aPTT) within normal limits

11. Patient must not have known history of metastatic CNS disease.

12. Female patients MUST NOT be pregnant or breastfeeding. Due to the unknown teratogenic properties of AVE0005 (VEGF Trap), its use in pregnant or breastfeeding patients is CONTRAINDICATED. For women of childbearing potential, a negative pregnancy test is required within 1 week prior to randomization.

13. Women of childbearing potential and sexually active males must agree to use an accepted and effective method of contraception while on this study, and for 6 months after the completion of the study.

14. Patients with basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix within the past five years must have been treated with curative intent. Patients with a history of prior malignancy are eligible provided they were treated with curative intent and

have been free of disease for >5 years.

15. Patient must not have any of the following conditions within 24 weeks prior to randomization:

myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, NYHA class III or IV congestive heart failure, cerebrovascular accident or transient ischemic attack.

16. Patients must not have had a prior pulmonary embolism, deep vein thrombosis, or other thromboembolic event.

17. Patient must not have a history of uncontrolled or labile hypertension (with or without antihypertensive drug treatment), defined as blood pressure >150/100 mm Hg or systolic blood pressure >180 mm Hg on at least 2 repeated determinations on separate days within 12 weeks prior to drug administration.

18. Patient must not have a history of any condition (social or medical) that, in the opinion of the investigator, might confound the results of the study or pose additional, unacceptable risk to the patient.

19. Patient must not have known, clinically s