Sunitinib Malate With or Without Gemcitabine Hydrochloride in Treating Patients With Advanced Kidney Cancer That Cannot Be Removed By Surgery

OBJECTIVES:

Primary

- To evaluate the response rate to sunitinib malate with vs without gemcitabine
hydrochloride in patients with advanced renal cell carcinoma with sarcomatoid features.

Secondary

- To evaluate progression-free survival of these patients.

- To evaluate overall survival of these patients.

- To describe the toxic effects of both sunitinib malate alone and in combination with
gemcitabine hydrochloride in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to risk (good risk
[clear cell and < 20% sarcomatoid and performance status (PS) 0] vs intermediate risk [20-50%
sarcomatoid and PS 0] vs poor risk [non-clear cell or > 50% sarcomatoid or PS 1 or non-clear
cell]). Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, 22,
and 29 and oral sunitinib malate once daily on days 1-14 and 22-35.

- Arm II: Patients receive oral sunitinib malate once daily on days 1-14 and 22-35.

In both arms, courses repeat every 42 days for up to 1 year in the absence of disease
progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and
then every 6 months for 1 year.

PROJECTED ACCRUAL: A total of 100 patients (60 in arm I and 40 in arm II) will be accrued to
this study.

DISEASE CHARACTERISTICS:

- Histologically confirmed* renal cell carcinoma

- Disease of any subtype allowed

- Disease must have sarcomatoid features NOTE: *Patients must have a
paraffin-embedded tumor specimen from the kidney or metastatic site available for
central review and confirmation of tumor histology

- No collecting duct or medullary carcinoma

- Measurable advanced disease that is not resectable by surgery

- Patients with resected or radiated brain metastases or those treated with stereotactic
radiation therapy are eligible, provided they have been off steroids for at least 2
weeks

PATIENT CHARACTERISTICS:

- ECOG performance status 0-2

- AGC ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Hemoglobin ≥ 9.0 g/dL (transfusions allowed)

- Serum creatinine clearance ≥ 30 mL/min

- SGOT and SGPT ≤ 2.5 times ULN (≤ 5 times ULN in the presence of liver metastases)

- Total bilirubin ≤ 1.5 times ULN

- Baseline QTc interval < 500 msec on EKG

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception before and during study treatment

- Able to swallow pills

- No history of stroke within the past 6 months

- No clinically significant cardiovascular disease, defined as one of the following:

- Uncontrolled hypertension (BP > 150/100 mm Hg at the time of enrollment)

- Patients with hypertension and BP ≤ 150/100 mm Hg on stable antihypertensive
regimen are eligible

- History of myocardial infarction or unstable angina within the past 24 weeks

- NYHA class II-IV congestive heart failure, serious cardiac arrhythmia requiring
medication, or unstable angina pectoris

- Peripheral vascular disease ≥ grade II

- No ongoing ventricular cardiac dysrhythmias ≥ grade 2 as assessed by NCI CTCAE version
4

- No patients with a history of serious ventricular arrhythmia (ventricular
tachycardia or ventricular fibrillation > 3 beats in a row)

- No patients with ongoing atrial fibrillation

- No pre-existing thyroid abnormality with thyroid-stimulating hormone that cannot be
maintained at less than or within the normal range with medication

- No serious concurrent illness or active infection that would jeopardize the ability of
the patient to receive study treatment

- No known HIV

- Patients with a history of prior malignancy are eligible provided they were treated
with curative intent and have been disease free for the time period considered
appropriate to not interfere with the outcome of this study

PRIOR CONCURRENT THERAPY:

- No prior systemic therapy for metastatic disease

- Patients who were randomized to placebo on an adjuvant study are eligible

- More than 2 weeks since prior radiotherapy and recovered

- Previously irradiated lesions must not be the sole site of disease

- More than 2 weeks since prior and no concurrent ketoconazole, dexamethasone,
dysrhythmic drugs (terfenadine, quinidine, procainamide, sotalol, probucol, bepridil,
indapamide, or flecainide), haloperidol, risperidone, rifampin, grapefruit, or
grapefruit juice

- Topical and inhaled steroids are allowed