Sunitinib Malate in Treating Patients With Previously Untreated Metastatic Kidney Cancer

PRIMARY OBJECTIVES:

I. To determine the feasibility of intermittent sunitinib therapy in patients with metastatic
renal cell carcinoma (RCC).

SECONDARY OBJECTIVES:

I. To determine the clinical outcome (response rate and overall progression-free survival) in
metastatic renal cell carcinoma patients treated with intermittent sunitinib therapy.

II. To evaluate the toxicity of intermittent sunitinib therapy in patients with metastatic
renal cell carcinoma.

III. To assess the feasibility of detecting circulating tumor cells (CTCs) in RCC patients
and investigate the association between the VEGF -634 genotype and the occurrence of
hypertension in sunitinib-treated RCC patients.

OUTLINE:

Patients receive oral sunitinib malate once daily on days 1-28. Sunitinib dosing schedule may
be changed to 14 days on followed by 7 days off, and repeated for a 6-week cycle, at the
discretion of the treating physician for toxicity purposes. Cycles will be defined as 6 week
intervals regardless of dosing interruptions. All patients will be treated for 4 cycles in
the absence of unacceptable toxicity or RECIST-defined progressive disease.

Inclusion Criteria:

- Histologically or cytologically-proven advanced RCC with a component of clear cell
histology

- Measurable disease per RECIST criteria

- ECOG performance status 0-1

- Prior nephrectomy is NOT required

- Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase [SGOT]) and
serum alanine transaminase (ALT; serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 x
laboratory upper limit of normal (ULN)

- Total serum bilirubin ≤ 2.0 x ULN

- Absolute neutrophil count (ANC) ≥ 1500/uL

- Platelets ≥ 100,000/uL

- Hemoglobin ≥ 8.0 g/dL (transfusion permitted)

- Serum calcium ≤ 12.0 mg/dL

- Serum creatinine ≤ 2.5 mg/dL

- Patients with history of brain metastases can be enrolled at a minimum of 2 weeks
following the completion of surgery, gamma knife or whole brain radiotherapy; repeat
brain MRI not required for eligibility

- Signed and dated informed consent document indicating that the patient (or legally
acceptable representative) has been informed of all pertinent aspects of the trial
prior to enrollment

Exclusion Criteria:

- Prior systemic treatment for advanced RCC. Prior adjuvant therapy (any drug) is
allowed if end of adjuvant therapy was more than 1 year prior to start of sunitinib on
this protocol.

- Any of the following within the 6 months prior to study drug administration:
myocardial infarction, severe/unstable angina, severe peripheral vascular disease
(claudication) or procedure on peripheral vasculature, coronary/peripheral artery
bypass graft, New York Heart Association grade II or greater congestive heart failure,
cerebrovascular accident or transient ischemic attack, clinically significant bleeding
or pulmonary embolism

- Hypertension that cannot be controlled by medications to < 160/90 mmHg

- Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome
(AIDS)-related illness

- Pregnancy or breastfeeding

- Other severe acute or chronic medical or psychiatric conditions or laboratory
abnormality that may increase the risk associated with study participation or study
drug administration, or may interfere with the interpretation of study results, and in
the judgment of the investigator would make the patient inappropriate for entry into
this study