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

This phase II trial studies how well pazopanib hydrochloride works in treating patients with advanced or progressive malignant pheochromocytoma or paraganglioma. Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

PRIMARY OBJECTIVES:

I. To assess the anti-tumor activity (in terms of the tumor response rate using the Response Evaluation Criteria in Solid Tumors \[RECIST\] criteria) of pazopanib (pazopanib hydrochloride) (GW786034) in patients with advanced malignant pheochromocytomas and paragangliomas.

SECONDARY OBJEC TIVES:

I. To assess safety profile of pazopanib. II. To assess duration of tumor response. III. To assess time to treatment failure. IV. To assess progression-free survival time. V. To assess overall survival time.

TERTIARY OBJECTIVES:

I. For patients with secretory tumors, to examine changes in urinary catecholamine and/or metanephrine levels.

II. For patients with secretory tumors, to examine whether pazopanib-induced changes in urinary catecholamine and/or metanephrine levels during the first cycle of treatment may be associated with objective tumor response.

III. To examine associations between tumor response and somatic mutational status in archived tumors, or germline mutational status in patient's peripheral blood mononuclear cells, (presence of succinate dehydrogenase complex subunit D \[SDHD\], succinate dehydrogenase complex subunit B \[SDHB\], ret proto-oncogene \[RET\], von Hippel-Lindau tumor suppressor \[VHL\], neurofibromatosis type-1).

IV. To examine associations between tumor response and tumor expression levels of angiogenic and vascular markers including hypoxia inducible factor 1, alpha (HIF-1a), vascular endothelial growth factor receptor (VEGF-R) (total and phospho-) and microvessel density in archival tumor tissue.

IV. To examine whether the extent of tumor response/regression may be correlated with plasma pazopanib (GW786034) concentration achieved after the third cycle (first cycle after run-in cycles) of pazopanib (GW786034) therapy.

OUTLINE:

Patients receive pazopanib hydrochloride orally (PO) once daily (QD) on days 1-28 (days 1-14 of courses 1 and 2). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients undergo urine and blood sample collection at baseline and periodically during study for correlative studies.

After completion of study therapy, patients are followed up every 3-6 months for up to 5 years.

Eligibility Criteria:
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)