Carfilzomib in Refractory Renal Cell Carcinoma (RCC)

Inclusion Criteria:

1. Biopsy proven clear cell kidney cancer with metastatic disease. Progressive disease or intolerance to at least one but not more than three (3) prior systemic therapy(ies)
2. Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>/= 20 mm with conventional techniques or as \>/= 10 mm with spiral CT scan.
3. Age \>/= 18 years
4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2
5. Adequate hepatic function with serum ALT and AST \</= 3.0 times the upper limit of normal and serum direct and total bilirubin \</= 1.5 times the upper limit of normal.
6. Absolute neutrophil count (ANC) \>/= 1.0 × 10\^9/L; patients with an ECOG performance status of 2 at study entry must have an ANC \>/= 1.5 x 10\^9/L
7. Hemoglobin \>/= 8 g/dL (80 g/L) within 14 days prior to beginning study treatment (subjects may be receiving red blood cell \[RBC\] transfusions in accordance with institutional guidelines); Patients with an ECOG performance status of 2 at study entry must have a hemoglobin \>/= 9 g/dL (transfusion assistance acceptable)
8. Platelet count \>/= 50 × 10\^9/L; Patients with an ECOG performance status of 2 at study entry must have a platelet count \>/= 100 × 10\^9/L
9. Creatinine clearance (CrCl) \>/= 30 mL/minute, either measured or calculated using a standard formula (eg, Cockcroft and Gault)
10. Written informed consent in accordance with federal, local, and institutional guidelines.
11. Females of childbearing potential (FCBP) must agree to ongoing pregnancy testing and to practice contraception during the study and for a period of 6 weeks after you stop receiving the study drug
12. Male subjects must agree to practice contraception during the study and for a period of 6 weeks after you stop receiving the study drug

Exclusion Criteria:

1. Brain metastases not controlled with surgery, whole brain radiotherapy, or with stereotactic radiosurgery
2. Systemic therapy within two weeks of treatment initiation
3. Pregnant or lactating females
4. Major surgery within 21 days prior to beginning study treatment
5. Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to beginning study treatment
6. Known human immunodeficiency virus infection
7. Active hepatitis B or C infection
8. Unstable angina or myocardial infarction within 4 months prior to beginning study treatment, NYHA Class III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless subject has a pacemaker
9. Uncontrolled hypertension (defined by BP consistently \> 150/100) or uncontrolled diabetes (defined by HbA1c \> 8.5) within 14 days prior to beginning study treatment
10. Nonhematologic malignancy within the past 2 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or less with stable prostate-specific antigen levels; or d) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder or benign tumors of the adrenal or pancreas
11. Significant neuropathy (Grades 3-4, or Grade 2 with pain) within 14 days prior to beginning study treatment
12. Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib)
13. Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to all anticoagulation and antiplatelet options, antiviral drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment
14. Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to beginning study treatment
15. Any other clinically significant medical disease or condition that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent