A Pilot Study of SBRT With Adjuvant Pazopanib for Renal Cell Cancer

Inclusion Criteria: * Patient is considered a poor surgical candidate for removal of a renal mass as determined by pre-operative assessment due to the following factors or various combinations thereof: * Significant comorbidity precluding ability to deliver anesthesia, without compromised ability to undergo systemic chemotherapy with pazopanib as deemed by the Urologist and Medical Oncologist * Medically documented contraindication for surgery due to religion or risk of blood transfusion * Size or location of tumor deemed high risk for surgical intervention by Urologist * Unacceptable risk for anesthesia, such as history of malignant hyperthermia * Any one of these factors may or may not constitute unresectability, but for consideration for this trial, the surgical and medical oncologist must agree that the particular constellation of findings for the patient under consideration would likely entail a low probability (\< 50%) that the tumor would be resectable (with negative margins) or that the potential morbidity associated with an attempt at surgical resection would not be clinically acceptable * The numerical thresholds noted above are only a guideline and the clinical judgment of the surgeon and medical oncologist will determine unresectability or if patient refuses surgery or other forms of local therapy; the histopathology for this cohort is limited to clear cell carcinoma of the kidney * Patient is able to give and sign study specific informed consent * Negative serum or urine pregnancy test within 72 hours prior to registration for women of childbearing potential and agrees to use contraception for the duration of the treatment cycle and for a minimum of 30-days following the end of therapy (a minimum estimate 95 days) * Patient has a pathologically confirmed diagnosis of clear cell RCC * Karnofsky status of ≥ 70% * Subject has no contraindication for computed tomography (CT) and/or magnetic resonance imaging (MRI) during screening and is able to complete a screening examination; CT and/or MRI within 6 months of screening is required * Patient has inadequate organ function as defined by: * Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase \[SGOT\]) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase \[SGPT\]) =\< 2.5 x laboratory upper limit of normal (ULN) * Total serum bilirubin \< 1.5 x ULN * Absolute neutrophil count (ANC) \> 1500/uL * Platelets \> 100,000/uL * Hemoglobin \> 9.0 g/dL (no transfusion permitted within 1 week) * Serum creatinine \< 2.5 mg/dL * Urine to protein to creatinine (UPC) ratio \< 1; if UPC \> 1, then a 24-hour urine protein must be assessed; subjects must have a 24-hour urine protein value \< 1 g to be eligible * Prothrombin time (PT) or international normalized ratio (INR) and partial thromboplastin time (PTT) \< 1.2 X upper limit of normal (ULN) Exclusion Criteria: * Any patient with active connective tissue disease such as lupus, dermatomyositis * Major psychiatric illness, which would prevent completion of treatment or interfere with follow-up * Prior dose of radiation overlapping the treatment field determined by a study Radiation Oncologist to represent unacceptable risk for additional radiation to be targeted to the field * Pregnant and lactating females, and unwillingness to use contraception; or male subject not willing to use contraception during and for 21 days after the last dose of pazopanib therapy * Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding (e.g. active peptic ulcer, ulcerative colitis, Crohn's disease, abdominal fistula) within prior 6 months * Clinically significant gastrointestinal abnormalities that may affect absorption (e.g. malabsorption syndrome, major resection of the stomach or small bowel) * Corrected QT interval (QTc) \> 480 msecs (record QTc correction method) * History of clinically significant cardiovascular condition with the past 6 months (e.g. angioplasty or stenting, myocardial infarction, unstable angina, bypass surgery, symptomatic peripheral arterial disease \[PAD\], class III or IV congestive heart failure) * History of cerebrovascular accident within the past 6 months (e.g. transient ischemic attack \[TIA\]) * Poorly controlled hypertension (systolic blood pressure \[SBP\] \>= 140 mmHg or diastolic blood pressure \[DBP\] \>= 90 mmHg); the initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry * Major surgery or trauma within 29 days prior to first dose of study drug and/or presence of any non-healing wound, fracture or ulcer (catheter placement is not major surgery) * Evidence of active bleeding or bleeding diathesis * Recent hemoptysis (\>= half teaspoon of red blood within 8 weeks before first dose of study drug) * Treatment with any other anti-cancer therapies (e.g. other radiation, surgery or tumor embolization) within the last 14 days prior to first dose of study drug; or chemotherapy, immunotherapy, biologic therapy, investigational or hormonal therapy within 14-days (or 5 half-lives of a drug whichever is longer) prior to the first dose of the study drug pazopanib