MRI in Predicting Response to Sunitinib Malate in Patients With Stage IV Kidney Cancer

OBJECTIVES:

Primary

- Correlate tumor vascular permeability by dynamic contrast-enhanced MRI (DCE MRI) with
clinical outcome in patients with stage IV renal cell carcinoma treated with sunitinib
malate.

- Correlate genetic and histologic characteristics of the primary tumor with vascular
permeability by DCE-MRI.

Secondary

- Correlate genetic and histologic characteristics of the primary tumor with clinical
outcome in patients treated with sunitinib malate.

- Collect tissue samples for potential future exploratory analyses of pharmacokinetic and
pharmacogenomic parameters.

OUTLINE: Patients receive oral sunitinib malate once daily on days 1-28. Treatment repeats
every 42 days in the absence of disease progression or unacceptable toxicity.

Patients undergo dynamic contrast-enhanced MRI at baseline and after the first 4 weeks of
sunitinib malate.

Blood samples are collected at baseline and periodically during study for pharmacokinetic
analysis and for analysis of angiogenic growth factor levels. Tumor tissue samples are
collected at baseline for mutation analysis and for assessment of angiogenesis histology by
IHC.

DISEASE CHARACTERISTICS:

- Histologically confirmed renal cell carcinoma

- Stage IV disease

- Has undergone nephrectomy

- Archival tumor tissue samples available

- No history or clinical evidence of brain metastasis

PATIENT CHARACTERISTICS:

- ECOG performance status 0-2

- WBC ≥ 3,000/mm^3

- Absolute granulocyte count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Serum creatinine ≤ 2.0 times upper limit of normal (ULN) OR creatinine clearance ≥ 40
mL/min

- Total bilirubin ≤ 1.5 times ULN (< 3.0 times ULN for patients with Gilbert's disease)

- AST and ALT ≤ 2.5 times ULN (≤ 5.0 times ULN for patients with liver metastases)

- INR ≤ 1.5

- PTT normal

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No pre-existing thyroid abnormality with thyroid-stimulating hormone that cannot be
maintained in the normal range with medication

- No hypertension that cannot be controlled with medication (i.e., diastolic blood
pressure ≥ 100 mm Hg despite optimal medical therapy)

- No cardiac dysrhythmias ≥ grade 2 by NCI CTCAE v3.0

- No concurrent serious illness including, but not limited to, the following:

- Ongoing or active infection requiring parenteral antibiotics

- Clinically significant cardiovascular disease (e.g., uncontrolled hypertension,
myocardial infarction, or unstable angina)

- NYHA class II-IV congestive heart failure

- Serious cardiac arrhythmia requiring medication

- Peripheral vascular disease ≥ grade 2 within the past year

- Psychiatric illness and/or social situation that would limit compliance with
study requirements

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No prior antiangiogenesis therapy

- Prior radiotherapy to a symptomatic site of metastatic disease is allowed

- At least 2 weeks since prior radiotherapy and recovered

- No other concurrent investigational therapies

- No concurrent cytochrome P450 enzyme-inducing antiepileptic drugs (e.g., phenytoin,
carbamazepine, or phenobarbital), rifampin, or St. John's wort