A Pilot Neoadjuvant Clinical Trial With Evaluation of Molecular Effects With Sorafenib Tosylate for Patients With Stage II or Greater Renal Cell Carcinoma

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Diagnosis of renal cell carcinoma (RCC) as confirmed by either of the following:

- Radiographic documentation by MRI or CT scan

- Histological evidence of primary RCC

- Stage II-IV disease, as defined by any of the following:

- T > 7 cm

- Renal vein involvement

- Local invasion

- Evidence of lymph node involvement

- Distant metastatic disease

- Deemed suitable for nephrectomy by a urologist

- No requirement for surgery earlier than 4 weeks from study entry

- No known brain metastasis

- Patients with neurological symptoms must undergo a CT scan or brain MRI to
exclude brain metastasis

PATIENT CHARACTERISTICS:

- ECOG performance status 0-1

- Hemoglobin ≥ 9.0 g/dL

- ANC ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Bilirubin ≤ 1.5 times upper limit of normal (ULN)

- ALT and AST ≤ 2.5 times ULN (≤ 5 times ULN for patients with liver involvement)

- Creatinine ≤ 2.5 times ULN or glomerular filtration rate ≥ 50 mL/min

- INR ≤ 1.5 AND PTT normal

- Stable INR required at baseline for patients on warfarin

- Not pregnant or nursing

- Negative pregnancy test

- Fertile women must use effective contraception

- Fertile men must use effective contraception during and for ≥ 2 months after the last
dose of sorafenib tosylate

- No other active primary malignancy except skin cancer

- No active coronary artery disease

- No active bleeding diathesis

- Closely monitored therapeutic anticoagulation allowed

- No cardiac disease, including any of the following:

- New York Heart Association class III-IV congestive heart failure

- Unstable angina (i.e., anginal symptoms at rest) or new onset angina (i.e.,
beginning within the past 3 months)

- Myocardial infarction within the past 6 months

- No cardiac ventricular arrhythmias requiring anti-arrhythmic therapy

- No uncontrolled hypertension, defined as systolic blood pressure (BP) > 150 mm Hg or
diastolic BP > 90 mm Hg, despite optimal medical management

- No known HIV infection or chronic hepatitis B or C

- No active, clinically serious infection > grade 2

- No thrombolic or embolic events, such as a cerebrovascular accident or transient
ischemic attacks, within the past 6 months

- No pulmonary hemorrhage or bleeding event ≥ grade 2 within the past 4 weeks (≥ grade
3 for any nonpulmonary hemorrhage or bleeding event)

- No serious nonhealing wound, ulcer, or bone fracture

- No significant traumatic injury within the past 4 weeks

- No known or suspected allergy to sorafenib tosylate or any agent given in the course
of this study

- No condition that impairs the patient's ability to swallow whole pills

- No malabsorption problem

PRIOR CONCURRENT THERAPY:

- No major surgery or open biopsy within the past 4 weeks

- Concurrent anticoagulation therapy (e.g., warfarin or heparin) allowed

- No other concurrent investigational or commercial agents or therapies for RCC

- No concurrent Hypericum perforatum (St. John's wort) or rifampin