| Eligibility |
Inclusion Criteria:
1. 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 </= 2cm in size each are considered N0.
2. Predominant clear cell histology on pre-treatment biopsy of the primary tumor.
3. Patient should be candidate for curative radical nephrectomy.
4. ECOG Performance Status 0-1.
5. Patient must provide signed informed consent.
6. Male or female, age >/= 18 years.
7. Adequate renal function: serum creatinine level </=1.5 x ULN or calculated creatinine
clearance (as estimated by GFR using the MDRD formula) is >/= 60 ml/min.
8. Adequate hepatic function: alkaline phosphatase </= 1.5 x ULN; total bilirubin, AST,
and ALT </= 1.5 x ULN; INR <1.3 (or <3 if on anticoagulant therapy).
9. Adequate bone marrow function: ANC >/= 1.5 x 10/ 9L; Platelets >/= 100 x 109/L; Hb >9
g/dL
10. Urinary protein <100 on urinalysis (equivalent to <2+ by urine dipstick). If
urinalysis 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 <2 g per
24 hours
11. No hormonal therapy, chemotherapy, immunotherapy, or any other systemic therapy for a
malignancy, in the 5 years prior to current study enrollment.
12. Women of childbearing potential (defined as a female subject who is not surgically
sterilized, not at least 1 year postmenopausal) must have negative urine or serum
pregnancy test within 4 weeks of enrollment and again on the day of starting therapy
and she and/or her partner must utilize birth control while on therapy.
13. Male (defined as a male subject who has not been surgically sterilized) or female
patients of child-producing potential must agree to use adequate contraception (e.g.
IUD, condom plus spermicide, diaphragm, or cervical cap plus spermicide) or medical
contraception: as of date of study enrollment and for at least 1 month after last dose
of axitinib. Subjects who are not currently sexually active must agree and consent to
use one of the above-mentioned methods should they become sexually active while
participating in the study.
Exclusion Criteria:
1. Evidence of metastatic disease, adjacent organ invasion, retroperitoneal adenopathy on
pre-treatment imaging. In addition, patients with inferior vena cava thrombi extending
to the atrium or with evidence of Budd-Chiari Syndrome (hepatic dysfunction) will not
be eligible for the protocol.
2. Patients who undergo embolization of their primary tumor.
3. Previous treatment for their primary renal tumor, including prior chemotherapy,
immunotherapy, targeted therapy, radiation therapy, cryotherapy, radiofrequency
ablation or embolization.
4. Active malignancies other than renal cell carcinoma and/or history of other malignancy
within the last 5 years, except for adequately treated cone-biopsied in situ carcinoma
of the cervix or basal or squamous cell carcinoma of the skin
5. Uncontrolled hypertension (BP>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.
6. 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).
7. 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).
8. Active gastrointestinal bleeding.
9. Malabsorption syndromes such as celiac disease, cystic fibrosis, inflammatory bowel
disease, systemic sclerosis, and carcinoid syndrome.
10. Known HIV or Hepatitis C status.
11. 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.
12. Active seizure disorder or evidence of brain metastases, spinal cord compression, or
carcinomatous meningitis.
13. A serious uncontrolled medical disorder or active infection that would impair their
ability to receive study treatment.
14. 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
15. Withdrawal of consent.
16. Unwillingness or inability to comply with mandated pretreatment biopsy or therapeutic
regimen.
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