Inclusion Criteria:

• Histologically or cytologically confirmed malignant secretory or non-secretory pheochromocytoma or paraganglioma that is unresectable and deemed inappropriate for alternative local regional therapeutic approaches
• Objective evidence of tumor progression ≤ 185 days prior to registration as assessed by:
  • Unequivocal progression of objectively measured disease on successive appropriate imaging (e.g. computed tomography [CT] scan); in cases of uncertainty of tumor progression, the principal investigator of the study will be available to assist in decisions
• Measurable disease defined as:
  • At least one non-nodal lesion whose longest diameter can be accurately measured as ≥ 2.0 cm with chest x-ray, or as ≥ 1.0 cm with CT scan, CT component of a positron emission tomography (PET)/CT, or magnetic resonance imaging (MRI); and/or
  • A lymph node whose short axis must be > 1.5 cm when assessed by CT scan (CT scan slice thickness recommended to be no greater than 5 mm)
  • Note: Tumor lesions in a previously irradiated area are not considered measurable disease
• Life expectancy > 24 weeks
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Leukocytes ≥ 3,000/uL
• Absolute neutrophil count ≥ 1,500/uL
• Platelets ≥ 100,000/uL
• Hemoglobin ≥ 9 g/dL (5.6 mmol/L); transfusions not permitted ≤ 7 days of registration
• Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (except in cases of Gilbert's syndrome, where indirect bilirubin may be elevated, but the direct bilirubin remains within 1.5 x ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 2.5 x ULN
• NOTE: Subjects who have both bilirubin > ULN and AST/ALT > ULN are not eligible
• Alkaline phosphatase ≤ 2.5 x ULN
• Creatinine ≤ 1.5 mg/dL (133 umol/L) or within normal institutional limits OR creatinine clearance ≥ 50 mL/min/1.73m^2 for subjects with creatinine levels about institutional normal
• Urine protein/creatinine ratio ≤ 1 OR 24-hour urine < 1 gram
• Prothrombin time (PT)/international normalized ratio (INR)/partial thromboplastin time (PTT) ≤ 1.2 x ULN unless a subject is receiving Coumadin and has stable INR which is in range for the desired level of anticoagulation
• Blood pressure (BP) < 140 mmHg (systolic) and < 90 mmHg (diastolic); initiation or adjustment of BP medication is permitted prior to registration provided that the average of three BP readings at a visit prior to registration is < 140/90 mmHg
  • NOTE: All patients with secretory pheochromocytomas or paragangliomas are required to: 1) be evaluated in consultation by a hypertension specialist (at the registering institution) with experience in the management of hypertension in the setting of catecholamine-secreting tumors (usually an endocrinologist, nephrologist, or a cardiologist), and in the setting of hormone-associated hypertension 2) receive alpha- and beta-adrenergic blockade for at least 7 days prior to initiation of pazopanib (GW786034); the hypertension specialist of record for each patient should be committed to following the patient during the clinical study with evaluation by said specialist required at all run-in cycle evaluations (cycles 1 and 2) and also after the first continuous dosing cycle (cycle 3) and thereafter on an as needed basis
• Negative serum pregnancy test done ≤ 7 days prior to registration, for women of childbearing potential only
• Ability to understand and the willingness to sign a written informed consent document
• Willingness to donate blood and tissue for correlative marker studies

Exclusion Criteria:

• Any of the following:
  • Pregnant women
  • Nursing women
  • Men or women of childbearing potential who are unwilling to employ adequate contraception NOTE: breastfeeding should be discontinued if the mother is treated with pazopanib (GW786034)
• Any of the following:
  • Chemotherapy/systemic therapy ≤ 4 weeks prior to registration
  • Radiotherapy ≤ 4 weeks prior to registration
  • Surgery ≤ 4 weeks prior to registration
  • Nitrosoureas or mitomycin C ≤ 6 weeks prior to registration
  • Those who have not recovered from adverse events due to agents administered more than 4 weeks earlier NOTE: Concurrent therapy with octreotide is allowed providing that tumor progression on this therapy has been demonstrated; concurrent therapy with bisphosphonates (e.g. zoledronic acid) or denosumab is also allowed.

NOTE: An unlimited number of prior chemotherapeutic or biologic therapies for malignant pheochromocytoma or paraganglioma is permitted; this includes prior anti-angiogenesis therapies such as tyrosine kinase inhibitors

• Any other ongoing investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to pazopanib (GW786034) or other agents used in the study
• Any of the following:
  • Corrected QT (QTc) prolongation (defined as a QTc interval ≥ 500 msecs)
  • Left ventricular ejection fraction (LVEF) < institutional lower limit of normal (LLN)
  • Frequent ventricular ectopy
  • Evidence of ongoing myocardial ischemia
• Receiving prohibited cytochrome P450 (CYP) interactive concomitant medications within 7 days prior to registration
• Any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow and retain pazopanib (GW786034)
• Receiving any medications or substances with risk of torsades de pointes; note: medications or substances with risk of torsades de pointes are prohibited; medications or substances with possible or conditional risk of torsades de pointes may be used while on study with extreme caution and careful monitoring; patients receiving these later cautionary agents must be monitored serially with electrocardiogram (ECG) weekly during the run-in and first cycle of therapy and at each evaluation thereafter NOTE: These medications should be discontinued or replaced with drugs that do not carry these risks, if possible
• Any of the following conditions:
  • Active peptic ulcer disease
  • Known intraluminal bowel metastatic lesions
  • Inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease) or other gastrointestinal conditions which increase the risk of perforation
  • History of new abdominal fistula, gastrointestinal perforation or intra-abdominal abscess ≤ 84 days prior to registration; enrollment of patients with chronic/canalized fistulous tracts (present for > 84 days) is allowed
  • Serious or non-healing wound, ulcer, or bone fracture
  • History of familial QTc prolongation syndrome
• Any of the following conditions ≤ 185 days prior to registration:
  • Cerebrovascular accident (CVA) or transient ischemic attack (TIA)
  • Cardiac arrhythmia
  • Admission for unstable angina
  • Cardiac angioplasty or stenting
  • Coronary artery bypass graft surgery
  • Pulmonary embolism, untreated deep venous thrombosis (DVT) or DVT which has been treated with therapeutic anticoagulation < 42 days
  • Arterial thrombosis
  • Symptomatic peripheral vascular disease
  • Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system
• Hemoptysis in excess of 2.5 mL (1/2 teaspoon) ≤ 60 days prior to registration
• Any of the following:
  • Known active and/or untreated brain metastases
  • Brain metastases requiring ongoing therapy (e.g. corticosteroids)
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy
• Require heparin other than low-molecular weight heparin
• Prior use of pazopanib (GW786034)