Pazopanib Hydrochloride in Treating Patients With Advanced or Progressive Malignant Pheochromocytoma or Paraganglioma

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)