RATIONALE: Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

PURPOSE: This phase II trial is studying how well bortezomib works in treating patients with metastatic kidney cancer.

OBJECTIVES:

Primary

• Determine, preliminarily, the efficacy of bortezomib in patients with metastatic non-clear cell renal cell carcinoma in terms of objective response rate after a minimum of 2 courses of treatment.

Secondary

• Correlate clinical response in these patients with baseline von Hippel-Lindau expression and nuclear factor-KB activity.

OUTLINE: This is an open-label study.

Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 1 month and then periodically for 2 years.

PROJECTED ACCRUAL: A total of 27 patients will be accrued for this study.

Inclusion Criteria:

• Histologically confirmed pure non-clear cell renal cell carcinoma (RCC)
• Distant metastatic disease (Tx, Nx, M1)
• Tumor expresses wild-type von Hippel-Lindau tumor suppressor gene/protein
• Measurable disease on imaging scan (≥ 1 cm)
• Brain metastases allowed provided they have been treated with surgery and/or radiation therapy and show no evidence of progression on cerebral CT or MRI scan 2 months following surgery and/or radiation therapy.
• Life expectancy ≥ 3 months
• Karnofsky performance status ≥ 60%
• Negative pregnancy test
• Fertile patients must use an acceptable method of contraception
• No other major illnesses likely to limit survival
• Platelet count ≥ 100,000/mm^3
• Absolute neutrophil count ≥ 1, 000/mm^3
• Hemoglobin ≥ 10 g/dL (transfusion allowed)
• Creatinine clearance ≥ 30 mL/min OR creatinine ≤ 2 mg/dL
• ALT or AST ≤ 2.5 times upper limit of normal
• At least 4 weeks since prior radiotherapy and recovered
• More than 30 days since any other prior investigational drugs

Exclusion Criteria:

• active CNS metastases
• pregnant or nursing
• myocardial infarction within the past 6 months
• New York Heart Association class III or IV heart failure
• uncontrolled angina
• severe uncontrolled ventricular arrhythmias
• electrocardiographic evidence of acute ischemia or active conduction system abnormalities
• Peripheral neuropathy ≤ grade 1
• hypersensitivity to bortezomib, boron, or mannitol
• history of a non-RCC malignancy within the past 5 years except basal cell carcinoma of the skin
• serious medical or psychiatric illness that would preclude study participation
• prior cytotoxic chemotherapy for this cancer
• other concurrent investigational therapy
• concurrent chemotherapy, immunotherapy, or hormonal therapy

Beginning of treatment through 30 days post last treatment.

Approval of several agents for management of renal cell carcinoma rendered accrual to this trial quite difficult.