Sunitinib Before and After Surgery in Treating Patients With Metastatic Kidney Cancer That Can Be Removed By Surgery

OBJECTIVES:

- To describe the gene expression of VEGF and non-VEGF angiogenic growth factor genes in
kidney cancer specimens from patients with metastatic renal cell carcinoma treated with
sunitinib malate.

- To describe the association between quantitative gene expression levels of VEGF and
non-VEGF angiogenic factors and clinical efficacy of this drug, as measured by
response, duration of response, and time to progression in these patients.

OUTLINE: Patients receive oral sunitinib malate once daily for 8 weeks. Within 2 weeks after
completion of neoadjuvant chemotherapy, patients undergo a nephrectomy and evaluation for
response to therapy. Beginning 4-8 weeks after surgery patients resume oral sunitinib malate
once daily for up to 12 months in the absence of disease progression or unacceptable
toxicity.

Patients with disease progression after 8 weeks of adjuvant treatment receive treatment off
study with other agents.

Viable (non-necrotic) tumor and non-tumor kidney tissue samples are obtained at the time of
nephrectomy for correlative biomarker studies. Tissue samples are analyzed for gene
expression of VEGF and non-VEGF angiogenic factors by real-time RT-PCR, western blot, and/or
IHC. Blood samples are obtained at baseline and at 4 and 8 weeks for evaluation of
circulating levels of VEGF and selected chemokines.

After completion of study therapy, patients are followed monthly.

DISEASE CHARACTERISTICS:

- Diagnosis of clear cell renal cell carcinoma

- Metastatic disease

- Primary tumor is considered amenable to surgery

- Measurable disease, defined as ≥ 1 lesion that can be accurately measured in ≥ 1
dimension (longest diameter to be recorded) as > 20 mm by conventional techniques or
as > 10 mm by spiral CT scan

- No untreated brain metastases

- Treated brain metastases allowed provided lesion has been stable on two
consecutive CT or MRI scans separated by ≥ 2 months

PATIENT CHARACTERISTICS:

- ECOG performance status 0-2

- Leukocytes ≥ 3,000/μL

- ANC ≥ 1,500/μL

- Platelet count ≥ 75,000/μL

- Hemoglobin ≥ 8.5 g/dL

- Total Bilirubin ≤ 2 times upper limits of normal (ULN)

- AST and ALT ≤ 2.5 times ULN

- Creatinine ≤ 2.5 times ULN

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Able to undergo nephrectomy and treatment with sunitinib malate

- No history of allergic reactions attributed to compounds of similar chemical or
biological composition to sunitinib malate

- No uncontrolled intercurrent illness including, but not limited to, any of the
following:

- Ongoing or active infection

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Cardiac arrhythmia

- Psychiatric illness/social situations that would limit compliance with study
requirements

PRIOR CONCURRENT THERAPY:

- No prior systemic treatment with sunitinib malate

- No other concurrent investigational agents

- No concurrent combination antiretroviral therapy for HIV-positive patients

- Concurrent medications or substances known to affect, or with the potential to
affect, the activity or pharmacokinetics of sunitinib malate allowed at the
discretion of the principal investigator