The goal of this clinical research study is to learn if axitinib can help to control kidney cancer. The safety of this drug will also be studied.

The Study Drug:

Axitinib is designed to decrease blood supply to the tumor, which may slow tumor growth.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will take axitinib by mouth 2 times a day every day for 12 weeks. The dose may be changed based on any side effects you may have. You should take the drug about 12 hours apart. You should take the pills at about the same time each day. If you vomit anytime after taking a dose, you must not "make it up" with an extra dose, but instead take the next dose as previously scheduled. Any missed dose may be taken late up to 3 hours before the next scheduled dose, otherwise, it should be skipped.

A blood pressure monitor will be given to each participant for home use. You will be given instructions and shown how to monitor your blood pressure.

You will be provided with a calendar to record the date and time of each dose, and your blood pressure reading before taking the drug. Missed doses should also be recorded. You must also bring the study drug bottle to each study visit so the research nurse can count any remaining pills.

A drug list will be given to you to record drugs taken within 4 weeks before you enrolled on the study and while on study. A new list will be provided during each clinic visit. You should not start a new prescription or over-the-counter drug before talking with the study doctor, except in the case of a medical emergency.

Study Visits:

At Week 1:

• You will be asked about any drugs you may be taking.
• Your performance status will be recorded.
• You will complete the questionnaire about kidney cancer care. This questionnaire will take about 5 minutes to complete.
• Women who are able to become pregnant will have a blood (about 1 teaspoon) or urine pregnancy test.

At Week 3:

• Your medical history will be recorded.
• You will have a physical exam.
• Your performance status will be recorded.
• You will have an ECG.
• Blood (about 2 tablespoons) will be drawn for routine testing to check your thyroid function.
• Urine (about 2 tablespoons) will be collected for routine testing.
• You will complete the questionnaire about kidney cancer care.

At Weeks 5 and 9, you will be called and asked if you have had any side effects. This call should take about 10 minutes.

At Weeks 7 and 12:

• Your medical history will be recorded.
• You will have a physical exam.
• Your performance status will be recorded.
• Blood (about 2 tablespoons) will be drawn for routine testing and to check your thyroid function.
• Urine (about 2 tablespoons) will be collected for routine testing.
• You will complete the questionnaire about kidney cancer care.
• You will have a CT scan of chest and abdomen to check the status of the disease.
• At Week 12 only, you will have an ECG.

At Week 13, you will have surgery to remove the kidney tumor. You will receive a separate consent form for this surgery.

At Week 19:

• Your medical history will be recorded.
• You will have a physical exam.
• Your performance status will be recorded.
• Blood (about 2 tablespoons) will be drawn for routine testing and to check your thyroid function.
• You will complete the questionnaire about kidney cancer care.
• You will have a CT scan of chest and abdomen to check the status of the disease.
• If you have been treated for high blood pressure while taking the drug, your blood pressure will be monitored and your blood pressure medication will be reduced. Once your blood pressure reaches a certain level, this will be managed by your primary care doctor.

After Week 19, every 4 months (+/- 2 weeks) for the first 1 year, every 6 months (+/- 2 weeks) for the third and fourth year, then every year (+/- 1 month) for a total of 5 years post surgery:

• Your medical history will be recorded.
• You will have a physical exam.
• Your performance status will be recorded.
• You will have a CT scan of the chest and abdomen to check the status of the disease.
• Blood (about 2 tablespoons) will be drawn for routine testing and to check your thyroid function.
• You will complete the questionnaire about kidney cancer care (only during the first 2 years).

Length of Study:

You will take axitinib for up to 12 weeks. You will stop taking axitinib earlier than expected if the disease gets worse or if you have severe side effects. In both cases, you will move on to surgery after axitinib has been stopped.

After surgery, you will be contacted by the study staff every 4 months (+/- 2 weeks) for 1 year, every 6 months (+/- 2 weeks) for the next 2 years and every 12 months (+/- 1 month) for 2 more years (for a total of 5 years after surgery).

This is an investigational study. Axitinib is FDA approved and commercially available to treat advanced kidney cancer in adults when 1 previous drug treatment for this disease has not worked. In this study, it is being used for research purposes.

Up to 40 patients will take part in this study. All will be enrolled at MD Anderson.

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 \

Adverse Events monitored/assessed up to 12 weeks. All-Cause Mortality monitored/assessed up to 5 years

No participant deaths reported throughout study.