Velcade and Sorafenib in Unresected or Metastatic Renal Cell Carcinoma

Inclusion Criteria:

Each patient must meet all of the following inclusion criteria to be enrolled in the study:

* Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
* Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
* Male subject agrees to use an acceptable method for contraception for the duration of the study.
* All patients, 18 years or older with cytologically confirmed clear cell renal with no prior chemotherapy are eligible.
* Patients must have a life expectancy of at least 12 weeks
* Patients must have a Zebroid performance of 0-2
* Patients should have adequate bone marrow function defined by an absolute peripheral granulocyte count of \> 1500 cells/mm3 and platelet count \> 100,000/mm3 and absence of a regular red blood cell transfusion requirement.
* Patients should have adequate hepatic function with a total bilirubin \< 2 mg/dl and Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic-pyruvic transaminase (SGPT) \< two times the upper limit of normal, and adequate renal function as defined by a Serum creatinine \< 1.5 x the upper limit of normal.

Exclusion Criteria:

Patients meeting any of the following exclusion criteria are not to be enrolled in the study:

* Patients with non-measurable disease.
* Patients who are unable to take medications orally.
* Patients with resectable renal cell carcinoma
* Patients with a history of Hepatitis B, or Hepatitis C
* Patients known to be Human Immunodeficiency Virus (HIV) positive
* Patients with poorly controlled diabetes mellitus
* Patients with poorly controlled hypertension or hypotension
* Chronic pulmonary disease and a diffusion capacity \< 50 %, or a forced vital capacity (FVC) or forced expiratory volume in 1 second (FEV1) of \<50%
* Severe renal impairment (Creatinine clearance \[CrCL\]\< 13 ml/min)
* Patients with known malabsorption syndromes.
* Patient has Grade 2 peripheral neuropathy within 14 days before enrollment.
* Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
* Patient has hypersensitivity to bortezomib, boron or mannitol or sorafenib.
* Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum B-human chorionic gonadotropin (B-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
* Patient has received other investigational drugs with 28 days before enrollment.
* Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
* Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.
* Patients may receive no other concurrent chemotherapy or radiation therapy (XRT) during this trial.
* Patients may not have received XRT within 4 weeks prior to the first treatment.