Inclusion Criteria:

• Histological confirmation of non-clear cell renal cancer (including chromophilic [papillary], chromophobic, oncocytic, sarcomatoid, collecting duct [Bellini's duct]) or medullary renal cell carcinoma
• Up to one prior treatment for metastatic non clear cell carcinoma is allowed prior to registration as long as the agent used to treat was not pazopanib
• Measurable or non-measurable metastatic disease
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
• Absolute neutrophil count (ANC) >= 1500
• Platelets (PLT) ≥ 100,000
• Hemoglobin (HgB) > 9.0 g/dL; NOTE: Subjects may not have had a transfusion within 7 days of registration)
• Total bilirubin < 1.5 x upper limit of normal (ULN)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 X ULN; NOTE: Concomitant elevations in bilirubin and ALT/AST above 1.0 x ULN is not permitted
• Urine protein to creatinine ratio (UPC) < 1; NOTE: 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) ≤ 1.2 X ULN; NOTE: Subjects receiving anticoagulant therapy are eligible if their INR is stable and within the recommended range for the desired level of anticoagulation
• A female is eligible to enter and participate in this study if she is of:
  • Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who has had:
    • A hysterectomy
    • A bilateral oophorectomy (ovariectomy)
    • A bilateral tubal ligation
    • Is post-menopausal
    • Subjects not using hormone replacement therapy (HRT) must have experienced total cessation of menses for ≥ 1 year and be greater than 45 years in age, OR, in questionable cases, have a follicle stimulating hormone (FSH) value > 40 mIU/mL and an estradiol value < 40 pg/mL (< 140 pmol/L)
    • Subjects using HRT must have experienced total cessation of menses for ≥ 1 year and be greater than 45 years of age OR have had documented evidence of menopause based on FSH and estradiol concentrations prior to initiation of HRT
  • Childbearing potential, including any female who has had a negative serum pregnancy test, ≤ 7 days prior to registration
  • Agrees to use adequate contraception; acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of the physician, are as follows:
    • Complete abstinence from sexual intercourse for 14 days before exposure to investigational product, through the dosing period, and for at least 21 days after the last dose of investigational product
    • Oral contraceptive, either combined or progestogen alone
    • Intrauterine device (IUD) or intrauterine system (IUS) with a documented failure rate of less than 1% per year
    • Male partner sterilization (vasectomy with documentation of azoospermia) prior to the female subject's entry into the study, and this male is the sole partner for that subject
    • Double barrier method: condom and an occlusive cap (diaphragm or cervical/vault caps) with a vaginal spermicidal agent (foam/gel/film/cream/suppository)
• Subjects must provide written informed consent prior to performance of study-specific procedures or assessments, and must be willing to comply with treatment and follow-up; procedures conducted as part of the subject's routine clinical management (e.g., blood count, imaging study) and obtained prior to signing of informed consent may be utilized for screening or baseline purposes provided these procedures are conducted as specified in the protocol
• Willing to return to Mayo Clinic enrolling institution for follow-up
• Willing to provide tissue samples for mandatory future unspecified correlative research purposes

Exclusion Criteria:

• Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
  • Nursing women
  • Pregnant women
  • Men or women of childbearing potential who are unwilling to employ adequate contraception
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
• Immunocompromised patients (other than that related to the use of corticosteroids) including patients known to be human immunodeficiency virus (HIV) positive
• Prior history of receiving pazopanib treatments
• Uncontrolled intercurrent illness including, but not limited to:
  • Ongoing or active infection
  • Symptomatic anemia, uncontrolled hypertension (defined as systolic blood pressure [SBP] of ≥ 140 mmHg or diastolic blood pressure [DBP] of >= 90mmHg)
  • Symptomatic congestive heart failure as defined by the New York Heart Association (NYHA); does not exclude class III congestive heart failure (CHF)
  • Previously treated with therapies that are known to negatively impact cardiac function (e.g. prior treatment with anthracyclines)
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Evidence of active bleeding or bleeding diathesis
  • Psychiatric illness/social situations that would limit compliance with study requirements
  • Or any other serious uncontrolled medical disorders in the opinion of the investigator
• History of cerebrovascular accident including transient ischemic attack (TIA), myocardial infarction, pulmonary embolism or untreated deep venous thrombosis (DVT), coronary artery bypass graft surgery within 6 months prior to registration; Note: Subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible
• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
• Other active malignancy ≤ 5 years prior to registration; EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: If there is a history or prior malignancy, they must not be receiving other specific treatment for their cancer
• History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for 6 months prior to first dose of study drug; screening with CNS imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI]) is required only if clinically indicated or if the subject has a history of CNS metastases
• Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:
  • Active peptic ulcer disease
  • Known intraluminal metastatic lesion/s with risk of bleeding
  • Inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), or other gastrointestinal conditions with increased risk of perforation
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess ≤ 28 days prior to registration
  • Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to:
    • Malabsorption syndrome
    • Major resection of the stomach or small bowel
• Corrected QT interval (QTc) > 480 msecs using Bazett's formula
• Receiving any medications or substances with risk of torsades de pointes; Note: medications or substances on the list "Drugs with Risk of Torsades de Pointes" are prohibited; medications or substances on the list "Drugs with Possible or Conditional Risk of Torsades de Pointes" may be used while on study with extreme caution and careful monitoring
• Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels and/or hemoptysis in excess of 2.5 mL (or one half teaspoon) =< 8 weeks of registration
• Treatment with any of the following anti-cancer therapies: radiation therapy, surgery or tumor embolization, chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy ≤ 14 days prior to registration
• Prior autologous or allogeneic organ or tissue transplantation
• Elective or planned major surgery to be performed during the course of the trial
• Receiving any medications or substances that are strong or moderate inhibitors of cytochrome P450 3A4 (CYP3A4); use of the strong or moderate inhibitors are prohibited =< 7 days prior to registration
• Receiving any medications or substances that are inducers of CYP3A4; use of inducers are prohibited ≤ 7 days prior to registration