Bortezomib 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