Sorafenib in Treating Patients With Metastatic or Unresectable Kidney Cancer

Inclusion Criteria:

• Histologically or cytologically confirmed renal cell carcinoma (RCC)

  • Must have a component of conventional clear cell RCC
  • Predominant clear cell component ≥ 75%
• Metastatic or unresectable 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)

• Measurable or nonmeasurable disease, includes any of the following:

  • Small lesions, 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
• Karnofsky performance status 70-100%
• 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
• At least 4 weeks since prior major surgery and/or radiotherapy and recovered
• 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

Exclusion Criteria:

• Patients with true papillary, sarcomatoid features without any clear cell component, chromophobe, oncocytoma, collecting duct tumors, or transitional cell carcinoma are not eligible
• No evidence of CNS metastases
• No imaging (MRI or CT scan of the brain) abnormality indicative of CNS metastases within past 42 days
• Not pregnant or nursing (negative pregnancy test)
• 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)
• No more than one prior systemic therapy for RCC
• No prior vascular endothelial growth factor receptor agents

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

  o Topical and/or inhaled steroids allowed

• No concurrent full-dose oral or parenteral anticoagulation

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