Bortezomib in Treating Patients With Metastatic Kidney Cancer

A Phase II Study of Bortezomib (Velcade ) Administered as a Single Agent in Metastatic Non-Clear Cell Renal Cell Carcinoma (RCC) Patients

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