| | Requirement |
| 1 | Distant metastatic (Tx Nx M1) or locally recurrent renal cell carcinoma not amenable to cure by surgical or other means. |
| 2 | Measurable or non-measurable (evaluable) disease either on imaging scan or PE. |
| 3 | Pathological confirmation of the diagnosis of renal cell carcinoma either at prior nephrectomy or by biopsy of a primary or metastatic lesion – provision of a paraffin-embedded tissue block to confirm the diagnosis and allow molecular correlate assessment is required. |
| 4 | ECOG PS 0 or 1. |
| 5 | AGC = / >1.5; platelets = / >100,000 (obtained within 28 days of registration). |
| 6 | Calculated or measured CrCl at least 40 ml/min (obtained within 28 days of registration). |
| 7 | Urine protein:creatinine ratio <1.0 at screening. |
| 8 | May have been treated with interleukin and/or interferon but must not have had >1 line of prior cytotoxic chemotherapy. |
| 9 | May have had up to 1 biologic therapy provided thay have not had bortezomib or bevacizumab. |
| 10 | May have had up to 2 prior vaccine therapies. |
| 11 | May have been treated with RT provided there are measurable or evaluable lesions outside of RT field and has recovered from the side effects of the therapy (typically 2 weeks after final fraction) and <30% of the total BM has been irradiated. |
| 12 | Signed informed consent (including HIPAA authorization). |
| 1 | Brain metastases or history of brain metastases. |
| 2 | History of DVT or thromboembolic disease within 1 year or requiring ongoing anti-coagulant therapy. |
| 3 | History of stroke or MI within 6 months. |
| 4 | Other major illnesses likely to limit survival, including poorly controlled HTN (BP >150/100 mmHg) or symptomatic or clinically significant PVD or angina pectoris. |
| 5 | Unstable angina. |
| 6 | NYHA Gr II or greater CHF. |
| 7 | Evidence of bleeding diathesis or coagulopathy. |
| 8 | Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to day 0, anticipation of need for major surgical procedure during the course of the study. |
| 9 | Minor surgical procedures, FNA, or core biopsies within 7 days prior to day 0. |
| 10 | Pregnant or breastfeeding women. Female patients of childbearing potential must have a negative serum ß-HCG pregnancy test during screening. Female patients must either be post-menopausal or surgically sterilized or be willing to use an acceptable method of birth control, i.e., hormonal contraceptive, IUD, diaphragm with spermicide, condom with spermicide, or abstinence, for the duration of the study. Pregnancy testing is not required for post-menopausal or surgically sterilized women. Male patients must agree to use an acceptable method for contraception for the duration of the study. |
| 11 | Inability to comply with study and/or follow-up procedures. |
| 12 | History of abdominal fistula, GI perforation, or intra-abdominal abscess within 28 days prior to day 0. |
| 13 | Serious, non-healing wound, ulcer, or bone fracture. |
| 14 | Neuropathy at baseline >Gr 1. |
| 15 | Prior other investigational drugs within 14 days before enrollment. |
| 16 | Hypersensitivity to bevacizumab, bortezomib, boron, or mannitol. |
