Neoadjuvant Axitinib in Locally Advanced Renal Cell Carcinoma (RCC)

Inclusion Criteria

• Locally advanced renal cell carcinoma without evidence of metastatic disease with absence of adjacent organ invasion or retroperitoneal adenopathy (cT2-T3b, N0, M0). Patients with retroperitoneal lymph nodes /= 18 years.
• Adequate renal function: serum creatinine level /= 60 ml/min.
• Adequate hepatic function: alkaline phosphatase /= 1.5 x 10/ 9L; Platelets >/= 100 x 109/L; Hb >9 g/dL
• Urinary protein /=100 (equivalent to dipstick is >/=2+) then a 24-hour urine collection can be done and the patient may enter only if urinary protein is 140/90 on medications), as documented by 2 baseline blood pressure readings taken at least 1 hour apart. The baseline systolic blood pressure readings must be </=140 mm Hg, and the baseline diastolic blood pressure readings must be </=90 mm Hg. Patients whose hypertension is controlled by antihypertensive therapies are eligible.
• Current use or anticipated need for treatment with drugs that are known potent CYP3A4 inhibitors (ie, grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, erythromycin, telithromycin, clarithromycin, indinavir, saquinavir, ritonavir, nelfinavir, nefazodone, lopinavir, atazanavir, amprenavir, fosamprenavir and delavirdine).
• Current use or anticipated need for treatment with drugs that are known potent CYP3A4 or CYP1A2 inducers (ie, carbamazepine, dexamethasone, felbamate, omeprazole, phenobarbital, phenytoin, amobarbital, nevirapine, primidone, rifabutin, rifampin, and St. John's wort).
• Active gastrointestinal bleeding.
• Malabsorption syndromes such as celiac disease, cystic fibrosis, inflammatory bowel disease, systemic sclerosis, and carcinoid syndrome.
• Known HIV or Hepatitis C status.
• Requirement of anticoagulant therapy with oral vitamin K antagonists. Low-dose anticoagulants for maintenance of patency of central venous access devise or prevention of deep venous thrombosis is allowed. Therapeutic use of low molecular weight heparin is allowed.
• Active seizure disorder or evidence of brain metastases, spinal cord compression, or carcinomatous meningitis.
• A serious uncontrolled medical disorder or active infection that would impair their ability to receive study treatment.
• Any of the following within the 12 months prior to study drug administration: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack and 6 months for deep vein thrombosis or pulmonary embolism
• Withdrawal of consent.
• Unwillingness or inability to comply with mandated pretreatment biopsy or therapeutic regimen.