Safety and Toxicity Study of Sorafenib in Patients With Kidney Cancer

Sorafenib to be administered as 28-day cycles.

Sorafenib dose escalation by cycle is:

• Cycle 1: 400 mg BID
• Cycle 2: 600 mg BID
• Cycle 3+: 800 mg BID

Within subject dose escalation and maximum dose is dependent on observed tolerability.

Dose escalation only occurs after acceptable tolerability is demonstrated by subject.

Inclusion criteria

• Histologically- or cytologically-confirmed metastatic or unresectable renal cell carcinoma (RCC).
• must have a component of conventional clear cell renal carcinoma.
• No more than one prior systemic therapy.
• No prior vascular endothelial growth factor receptor agents.
• Prior palliative radiotherapy in metastatic lesion(s) is permitted, provided the subject has at least one measurable and/or evaluable lesion(s) that has not been irradiated.
• All major surgery of any type and/or radiotherapy must be completed at least 4 weeks prior to Day 1 dosing. Patients must have recovered from surgery and/or radiotherapy toxicity prior to Day 1 dosing.
• Measureable disease by RECIST criteria
• Karnofsky performance status at least 70% or ECOG not more than 2
• Ability to give written informed consent
• At least 18 years old
• Negative pregnancy test within 7 days of Day 1 dosing (female subjects of childbearing potential)
• Sexually active fertile subjects must agree to use an accepted method of contraception during the course of the study for 3 months thereafter.
• ANC at least 1,500/uL
• Platelet count at least 100,000/uL
• AST/ALT not more than 2.5 times the upper limit of normal (ULN)
• Alkaline phosphatase not more than 2.5 x ULN
• Serum bilirubin not more than 1.5 x ULN
• Amylase/Lipase within normal range
• Urinalysis not more than 1+ protein
• Serum creatinine not more than 1.5 x ULN
• No active ischemia by ECG
• Echocardiogram or MUGA ejection fraction at least 40%

Exclusion criteria

• Ongoing hemoptysis
• Cerebrovascular accident within 12 months
• Peripheral vascular disease with claudication on less than 1 block
• History of clinically significant bleeding
• Malignancy with true papillary/sarcomatoid features without any clear cell component
• Chromophobe
• Oncocytoma
• Collecting duct tumors
• Transitional cell carcinoma
• Deep venous thrombosis or pulmonary embolus within one year of consent
• Ongoing need for full-dose oral or parenteral anticoagulation. Low dose coumadin (1 mg) for maintenance of catheter patency or daily prophylactic aspirin is allowed
• Subjects with evidence of current central nervous system (CNS) metastases
• MRI or CT scan of the brain (with contrast, if possible) within 28 days prior to Day 1 dosing
• Significant cardiovascular disease defined as congestive heart failure (New York Heart Association Class II, II or IV)
• Angina pectoris requiring nitrate therapy
• Myocardial infarction within the last 6 months
• Uncontrolled hypertension (defined as blood pressure at least 160 mmHg systolic or at least 90 mmHg diastolic on medication)
• Ongoing requirement for systemic corticosteroid therapy (except replacement therapy for adrenal insufficiency). Topical and/or inhaled steroids are allowed.
• Uncontrolled psychiatric disorder
• Delayed healing of wounds, ulcers, and/or bone fractures
• Prior malignancy (EXCEPTIONS: adequately-treated basal cell or squamous cell skin cancer or any other cancer for which chemotherapy has been completed > 5 years ago and from which the patient has been disease-free for > 5 years)
• Pregnant
• Currently lactating
• Currently using St John's Wort (an herb)