Randomized, Double-Blind Phase III Study of Pazopanib vs. Placebo in Patients With Metastatic Renal Cell Carcinoma Who Have No Evidence of Disease Following Metastatectomy

• Patient must be at least 18 years of age at the time of randomization

• Patient must have pathologically confirmed renal cell carcinoma with a clear cell component; pure papillary and chromophobe histologies are excluded; there must be pathologic confirmation of metastatic disease in the resected metastasectomy specimen

• Patient must have undergone nephrectomy or partial nephrectomy to remove primary renal cell carcinoma (at any time in the past)

• Patient must have undergone surgical resection to remove one or more sites of metastatic disease, with successful removal of all known sites 2-12 weeks prior to randomization. Any number of prior metastasectomies may have been performed in the past, so long as the most recent procedure was within the 12 weeks of registration. The most recent procedure may be nephrectomy for a renal primary tumor

• Patients with synchronous disease at initial diagnosis must have metastatic (M1) disease (American Joint Committee on Cancer \[AJCC\] 7th edition T1-4N0-1M1)

• Positive surgical margins are permitted if the surgeon confirms complete resection of gross metastatic disease, and post-operative scans are negative

• Patients presenting with metachronous disease may have distant metastases, regional lymph node or renal bed recurrence. Recurrences at a partial nephrectomy resection site are not eligible if it is the only site of disease

• Patient must have no evidence of disease on post-operative imaging:

‣ A computed tomography (CT) of the chest must be obtained within 4 weeks prior to randomization with or without contrast

⁃ A CT of the abdomen/pelvis must be obtained within 4 weeks prior to randomization with intravenous (IV) contrast (oral contrast may be added at the radiologist's discretion); an magnetic resonance imaging (MRI) of the abdomen/pelvis with gadolinium may be substituted for the CT if the CT with IV contrast is contra-indicated

⁃ An MRI of the brain with and without gadolinium must be done within 8 weeks prior to randomization; a CT of the brain with and without IV contrast is permitted if MRI is contra-indicated (i.e., pacemaker)

• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at the time of randomization

• Absolute granulocyte count \> 1,500/mcL (within 2 weeks prior to randomization)

• Platelets \> 100,000/mcL (within 2 weeks prior to randomization)

• Total bilirubin \< 1.5 x institutional upper limit of normal (ULN) (within 2 weeks prior to randomization)

• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) \< 2.5 x upper limit of normal (ULN) (within 2 weeks prior to randomization)

• Calculated creatinine clearance (CrCl) \> 30 mL/min (within 2 weeks prior to randomization)

• Subjects must have a urine protein/creatinine (UPC) ratio \< 1; if UPC \>= 1, then a 24-hour urine total protein must be obtained; subjects must have a 24-hour urine protein value \< 1 g to be eligible; use of urine dipstick for renal function assessment is not acceptable (within 2 weeks prior to randomization)

• All females of childbearing potential must have a blood test or urine study within 2 weeks prior to randomization to rule out pregnancy; a female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)

• Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception or to abstain from sexual intercourse for the duration of their participation in the study; should a woman become pregnant while participating in this study, she should inform her treating physician immediately; if a man impregnates a woman while participating in this study, he should inform his treating physician immediately

• Patient must be able to swallow pills and have no significant impairment in gastrointestinal absorption including history of gastric bypass surgery

• Patient must have a corrected QT (QTc) interval on electrocardiogram (ECG) =\< 0.48 seconds by Bazett's calculation (=\< Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v.\]4 grade 2) prior to randomization

• Patient must have a systolic blood pressure =\< 140 mmHg and diastolic blood pressure must be =\< 90 mmHg, measured within 4 weeks prior to randomization; initiation or adjustment of anti-hypertensives prior to starting study treatment is allowed

• Patient must have no history of cerebrovascular accident (CVA) within 6 months of randomization