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
• Measurable disease
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
• Life expectancy > 24 weeks
• Absolute neutrophil count (ANC) ≥ 1500/mm^3
• White blood cell (WBC) count ≥ 3,000/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9.0 g/dL (5.6 mmol/L); NOTE: transfusions are not allowed ≤ 7 days prior to registration
• Total bilirubin ≤ 1.5 X upper limit of normal (ULN) (or total bilirubin ≤ 3.0 X ULN with direct bilirubin ≤ 1.5 X ULN in patients with well-documented Gilbert's Syndrome)
• Aspartate transaminase (AST/serum glutamic oxaloacetic transaminase [SGOT]) ≤ 2.5 X ULN
• Creatinine ≤ 1.5 mg/dL (133 umol/L) or ≤ ULN OR calculated creatinine clearance ≥ 30 mL/min/1.73m^2 for patients with creatinine levels above ULN
• Urine protein/creatinine ratio ≤ 1 OR 24-hour urine protein < 1.5 gram
• Negative pregnancy test done ≤ 7 days prior to registration, for women of childbearing potential only
• Blood pressure (BP) < 150 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 < 150/90 mmHg; NOTE: all patients with secretory pheochromocytoma or paraganglioma are REQUIRED to: 1) be evaluated in consultation by a hypertension specialist with specific 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) receive alpha- and beta-adrenergic blockade for at least 7-14 days prior to initiation of lenvatinib; the hypertension specialist of record for each patient should be committed to closely following the patient during the clinical study with evaluation by said specialist required at cycle 1 and 2 and thereafter on an as needed basis
• Provide written informed consent
• Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
• Ability to complete questionnaire(s) by themselves or with assistance

Exclusion Criteria:

• Any of the following:
  • Pregnant women
  • Nursing women
  • Men or women of childbearing potential who are unwilling to employ adequate contraception
• Chemotherapy/systemic therapy, radiotherapy, immunotherapy or surgery ≤ 21 days prior to registration or kinase inhibitor therapy ≤ 14 days prior to registration or failure to recover from toxicities (to grade 1 or below) from treatment; 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
• Active or uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Receiving any other investigational agent
• Current use of warfarin for any reason; NOTE: if patient can be safely transitioned to another anticoagulant, they may be eligible provided other criteria are satisfied
• Any of the following:
  • Correct QT (QTc) prolongation (defined as a QTc interval ≥ 500 msecs)
  • Left ventricular ejection fraction (LVEF) < institutional lower limits of normal (LLN)
  • Frequent ventricular ectopy
  • Evidence of ongoing myocardial ischemia
• Receiving any medications or substances with risk of torsades de pointes; NOTE: medications or substances with known risk of torsades de pointes are prohibited; consult pharmacist for review if needed
• Known active and/or untreated brain metastases
• Known severe allergic or other prohibitive reactions to other tyrosine kinase inhibitors (TKI)
• Prior treatment with lenvatinib
• Any of the following conditions:
  • Active peptic ulcer disease
  • 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; NOTE: 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 ≤ 6 months prior to registration:
  • Cerebrovascular accident (CVA) or transient ischemic attack (TIA)
  • Serious or unstable cardiac arrhythmia
  • Admission for unstable angina or myocardial infarction
  • 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 ≤ 30 days
  • Arterial thrombosis
  • Symptomatic peripheral vascular disease
• Other active malignancy ≤ 2 years prior to registration; EXCEPTIONS: non-melanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: if there is a history of prior malignancy, they must not be receiving other specific treatment for their cancer; NOTE: adjuvant anti-estrogen/hormonal therapy for breast cancer is allowed