The goal of this clinical research study is to learn more about the safety of giving sunitinib to patients with metastatic kidney cancer for 2 weeks followed by 1 week in which they receive no drug. Researchers want to learn more about the side effects of the drug and the effects of a different dosing schedule.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will take sunitinib capsules by mouth every day for 2 weeks, followed by 1 week in which you do not receive any study drug. This will then be repeated every 3 weeks.

Every 6 weeks will be 1 study cycle.

If you have any side effects tell the study doctor right away. The study doctor may change your dose of the study drug.

Study Visits:

Every day during the first week, and then at least 1 time each week during the study, your blood pressure will be checked (either at home, at the clinic, or by your local doctor). You will need to write down your blood pressure in a blood pressure diary each time you check it and bring the diary with you to each clinic visit.

On Day 1 of Cycle 1:

• You will have a physical exam.
• Blood (about 3-4 tablespoons) will be drawn for routine and biomarker testing.
• You will fill out a questionnaire about the quality of your life and about how you are feeling. This should take about 5 minutes.

On Day 42 of every cycle:

• You will have a physical exam.
• Blood (about 3-4 tablespoons) will be drawn for routine tests.

On Day 42 of every even-numbered cycle (Cycles 2, 4, 6, and so on):

• You will have a CT scan of your chest, abdomen, and pelvis.
• Blood (about 1 tablespoon) will be drawn to check your thyroid function.
• Blood (about 2 tablespoons) will be drawn for biomarker testing. (Cycles 2 , 4, and 6 only)
• You will fill out the questionnaire about the quality of your life and about how you are feeling. (Cycles 2 , 4, and 6 only)

At any time that the doctor thinks it is needed, additional blood (about 1 tablespoon) may be drawn to check your thyroid function, and you may need to have a bone scan and CT scan or MRI of the brain to check the status of the disease.

Length of Study:

You may continue taking the study drug for as long as the study doctor thinks it is in your best interest. You will be taken off treatment if the disease gets worse, intolerable side effects occur, or if you are unable to follow study directions.

Your participation in this study will be over after the follow-up visit. However, the study team may perform a medical record review or follow-up call to check on how you are doing. If you are called, this should last about 5-10 minutes.

End-of-Treatment Visit:

After you are no longer receiving the study drug, you will have an end-of-treatment visit. You will have a physical exam and blood (about 3-4 tablespoons) will be drawn for routine and biomarker testing.

End-of- Treatment Follow-Up Visit:

About 30 days after your end-of-treatment visit you will have a follow-up visit and the following procedures will be performed:

• You will have a physical exam.
• Blood (about 3-4 tablespoons) will be drawn for routine tests.
• You will have CT scans of your chest, abdomen and pelvis to check the status of the disease.

This is an investigational study. Sunitinib is FDA approved and commercially available to treat advanced kidney cancer. The dosing schedule being used on this study is investigational.

Up to 60 participants will be enrolled in this study. Up to 60 may take part at MD Anderson.

Inclusion Criteria:

1. Histologically or cytologically-confirmed metastatic renal cell carcinoma of clear cell histology. Prior nephrectomy is not a requirement for eligibility
2. Age >/=18 years
3. Measurable or evaluable metastatic disease per RECIST v 1
4. ECOG performance status 0-1
5. Normal organ and bone marrow function as defined by: Serum aspartate transaminase (AST) or serum glutamic oxaloacetic transaminase (SGOT) and serum alanine transaminase (ALT) or serum glutamic pyruvic transaminase (SGPT) </= 2.5 x laboratory upper limit of normal (ULN); Total serum bilirubin </= 2.0 x ULN; Absolute neutrophil count (ANC) >/= 1500/µL; Platelets >/= 100,000/µL; Hemoglobin >/= 9.0 g/dL (transfusion permitted); Serum calcium </= 12.0 mg/dL; Serum creatinine </= 2.5 mg/dL
6. Patients with a history of deep venous thromboembolism or pulmonary embolism on treatment with anticoagulation are eligible for the study.
7. Subjects must have the ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

1. Prior treatment with sunitinib or any other systemic therapy in the metastatic setting (prior neo/adjuvant therapy will be allowed if completed > 6 months prior to registration and therapy not discontinued for toxicity)
2. Uncontrolled hypertension (defined as blood pressure >140/90 mm Hg not controlled with anti-hypertensives)
3. Prior intraabdominal, intrathoracic, vascular, spinal or intracranial surgery or radiation therapy within 4 weeks of starting treatment
4. History of or known brain metastases, spinal cord compression, or carcinomatous meningitis
5. New York Heart Association (NYHA) grade II or greater congestive heart failure
6. Current treatment on another therapeutic clinical trial
7. Any of the following within the preceding 6 months- myocardial infarction, severe/unstable angina, severe peripheral vascular disease (claudication) or procedure on peripheral vasculature, coronary/peripheral artery bypass, graft, cerebrovascular accident or transient ischemic attack, clinically significant bleeding
8. Pregnant or breastfeeding women are excluded from this study because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with sunitinib. Breastfeeding must be discontinued if the mother is treated with sunitinib
9. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness
10. HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with sunitinib. In addition, these patients are at increased risk of lethal infections when treated with marrow suppressive therapy

Toxicities were monitored from the first dose until 30 days after the last dose of study drug was given, monitoring was approximately 36 months.