Sorafenib in Treating Patients With Metastatic or Unresectable Kidney Cancer

OBJECTIVES:

Primary

- Evaluate the safety and toxicity of dose escalating sorafenib tosylate in patients with
metastatic or unresectable renal cell carcinoma.

Secondary

- Determine tumor response in these patients.

- Determine time to progression in these patients.

- Determine overall survival of these patients.

Tertiary

- Collect data on angiogenesis inhibition induced by sorafenib tosylate.

- Collect data on immunomodulatory effects of sorafenib tosylate.

OUTLINE: This is an open-label study.

Patients receive oral sorafenib tosylate twice daily on days 1-28. Treatment repeats every 4
weeks for at least 2 courses in the absence of disease progression or unacceptable toxicity.

Patients receive escalating doses of sorafenib tosylate (in the absence of grade 3 or 4
dose-limiting toxicity) until a pre-determined dose is reached.

Blood and urine samples are collected at baseline and periodically during study for VEGF
level determination. Blood samples are analyzed for T4/T8, NK, CD25+, and Fox p3 by flow
cytometry. Tumor tissue blocks or unstained slides are obtained for chemistry staining of
VEGF.

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed renal cell carcinoma (RCC)

- Must have a component of conventional clear cell RCC

- Predominant clear cell component ≥ 75%

- Patients with true papillary, sarcomatoid features without any clear cell
component, chromophobe, oncocytoma, collecting duct tumors, or transitional cell
carcinoma are not eligible

- Metastatic or unresectable disease

- Measurable or nonmeasurable disease

- Measurable disease is defined as any lesion that can be accurately measured in at
least one dimension (longest diameter to be recorded) as ≥ 20 mm by conventional
techniques or ≥ 10 mm by spiral CT scan or MRI

- Nonmeasurable disease includes any of the following:

- Small lesions with longest diameter < 20 mm by conventional techniques or <
10 mm by spiral CT scan

- Bone lesions

- Leptomeningeal disease

- Ascites

- Pleural/pericardial effusion

- Lymphangitis cutis/pulmonitis

- Abdominal masses that are not confirmed and followed by imaging techniques

- Cystic lesions

- Irradiated lesions, unless progression is documented after radiotherapy

- Paraffin RCC tissue blocks or unstained slides must be obtained for future chemistry
staining of VEGF

- No evidence of CNS metastases

- No imaging (MRI or CT scan of the brain) abnormality indicative of CNS metastases
within the past 42 days

PATIENT CHARACTERISTICS:

- Karnofsky performance status 70-100%

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception (hormonal and/or barrier method)
during and for 3 months after completion of study treatment

- Granulocyte count ≥ 1,500/µL

- Platelet count ≥ 100,000/µL

- AST/ALT ≤ 2.5 times upper limit of normal (ULN)

- Alkaline phosphatase ≤ 2.5 times ULN

- Serum bilirubin ≤ 1.5 times ULN

- Protein ≤ 1+ by urinalysis

- Creatinine ≤ 1.5 times ULN

- No ongoing hemoptysis

- No cerebrovascular accident within the past 12 months

- No peripheral vascular disease with claudication while walking less than 1 block

- No history of clinically significant bleeding

- No deep venous thrombosis or pulmonary embolus within the past year

- No significant cardiovascular disease, defined as NYHA class II-IV congestive heart
failure, angina pectoris requiring nitrate therapy, or myocardial infarction within
the past 6 months

- No uncontrolled hypertension, defined as systolic BP > 160 mm Hg and/or diastolic BP >
90 mm Hg while on medication

- No preexisting thyroid abnormality whose thyroid function cannot be maintained in the
normal range by medication

- No uncontrolled psychiatric disorder

- No delayed healing of wounds, ulcers, and/or bone fractures

- No currently active second malignancy except nonmelanoma skin cancer

- Patients are not considered to have a 'currently active' malignancy if they have
completed anticancer therapy and are considered by their physician to be at less
than 30% risk of relapse

PRIOR CONCURRENT THERAPY:

- At least 4 weeks since prior major surgery and/or radiotherapy and recovered

- No more than one prior systemic therapy for RCC

- No prior vascular endothelial growth factor receptor agents

- Prior palliative radiotherapy for metastatic lesion(s) allowed provided there is at
least one measurable and/or evaluable lesion(s) that has not been irradiated

- More than 4 weeks since prior and no other concurrent anticancer therapy

- Concurrent continuation of bisphosphonates allowed for bone metastases prophylaxis

- No concurrent systemic corticosteroid therapy (except replacement therapy for adrenal
insufficiency)

- Topical and/or inhaled steroids allowed

- No concurrent full-dose oral or parenteral anticoagulation

- Low-dose warfarin (1 mg) for maintenance of catheter patency or daily
prophylactic aspirin allowed

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

- No concurrent ketoconazole, itraconazole, ritonavir, rifampin, or products containing
grapefruit juice

- No concurrent hormonal therapy or chemotherapy

- Concurrent hormones administered for non-disease related conditions (e.g.,
insulin for diabetes) allowed