Randomized Study of Sorafenib Dose Escalation in Patients With Previously Untreated Metastatic Renal Cell Carcinoma

Exclusion Criteria

• •Prior systemic anticancer treatment for metastatic disease, including investigational therapy.
• •Prior treatment with bevacizumab, sunitinib, or sorafenib even in the adjuvant setting.
• •Prior cytokine therapy with interleukin (IL)-2 or interferon (IFN) for metastatic disease.
• •Active malignancy other than RCC (except non-melanoma skin cancer) within 5 years of enrollment.
• •Hemodialysis or peritoneal dialysis.
• •Treatment with radiotherapy within 2 weeks of enrollment.
• •Cardiac disease: Congestive heart failure Class II or higher per NYHA. Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.
• •Uncontrolled CNS metastases. All patients must undergo a CT) scan/MRI of the brain to exclude brain metastasis. Patients with adequately treated CNS disease may be considered for participation as long as the first dose of sorafenib is 4 weeks after completion of CNS therapy.
• •Uncontrolled hypertension defined as SBP \> 150 mmHg or DBP \> 90 mmHg, despite optimal medical management.
• •Active clinically serious infection \> Grade 2 per the CTCAE v3.
• •Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
• •Pulmonary hemorrhage/bleeding event ≥ Grade 2 per CTCAE v3.0 within 4 weeks of administration of the first dose of study drug.
• •Any other hemorrhage/bleeding event ≥ Grade 3 per CTCAE v3.0 within 4 weeks of administration of the first dose of study drug.
• •Serious non-healing wound, ulcer, or bone fracture.
• •Evidence or history of bleeding diathesis or coagulopathy.
• •Major surgery, open biopsy or significant traumatic injury within 4 weeks of administration of the first study drug dose.
• •Use of St. John's Wort, rifampin (rifampicin), phenytoin, Phenobarbital, carbamazepine, dexamethasone.
• •Known or suspected allergy to sorafenib or any agent given in the course of this trial.
• •Any condition that impairs patient's ability to swallow whole pills.
• •Any malabsorption problem.
• •Pregnancy or lactation.