Bortezomib in Treating Patients With Metastatic Kidney Cancer

Phase 2

Completed

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Velcade	bortezomib	Velcade IV twice a week for two weeks on Days 1, 4, 8 and 11 of each cycle. A 10 day-rest period (Days 12-21) with no Velcade will follow the 2 weeks of treatment in each cycle. one cycle = 21 days

Primary Outcome Measures