Phase II Study of Axitinib (AG-013736) With Evaluation of the VEGF-pathway in Metastatic, Recurrent or Primary Unresectable Pheochromocytoma/Paraganglioma

* INCLUSION CRITERIA 2.1.1 Adults with a confirmed pathologic diagnosis of pheochromocytoma/paraganglioma by the Laboratory of Pathology, National Cancer Institute (NCI) when such tissue is available to confirm or In the event that outside tissue is not available: * an outside pathology report confirms the diagnosis of Pheo-PGI, AND * the patient has nuclear medicine imaging studies that would only be positive in an adult patient with a diagnosis of Pheo/PGL (Fluorodopa (F-DOPA), Dotatate, F-Dopamine or Metaiodobenzylguanidine (MIBG)) 2.1.1.1 Imaging confirmation of metastatic disease 2.1.1.2 Measurable disease at the time of enrollment per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. 2.1.1.3 A life expectancy of at least 3 months and Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 2.1.1.4 Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of Axitinib in patients \<18 years of age, children are excluded from this study, but will be eligible for future pediatric trials. 2.1.1.5 Information available or pending regarding possible genetic alterations that can explain the patient's pheochromocytoma/paraganglioma (mutations in succinate dehydrogenase-B (SDHB), SDHV or Von Hippel-Lindau (VHL) genes) 2.1.1.6 Last dose of chemotherapy or experimental therapy more than 4 weeks (6 weeks in the case of nitrosourea) prior to enrollment date; 2 weeks if the last therapy was received as part of a phase 0 or exploratory Investigational New Drug (IND) trial. Last surgery more than 4 weeks prior to enrollment, to allow for wound healing. Core biopsies or fine needle aspiration (FNA) will not require any waiting period 2.1.1.7 Last radiotherapy treatment greater than or equal to 4 weeks prior to starting treatment with this protocol and there must be sites of measurable disease that did not receive radiation 2.1.1.8 Prior therapeutic Metaiodobenzylguanidine (MIBG) is allowed 2.1.1.9 Organ and marrow function as defined below: 2.1.1.10 Total bilirubin less than or equal to 1.5 x upper limit of normal (ULN) (upper limit of normal), unless the patient meets the criteria for Gilbert's Syndrome. The upper limit value for bilirubin for subjects with Gilbert's Syndrome is less than 3 mg/dl. Note: A diagnosis of Gilbert's disease will be made in the presence of (1) unconjugated hyperbilirubinemia noted on several occasions; (2) normal results from complete blood count (CBC) count, reticulocyte count, and blood smear; (3) normal liver function test results; and (4) an absence of other disease processes that can explain the unconjugated hyperbilirubinemia. 2.1.1.11 Aspartate aminotransferase (AST) less than or equal to 2.5 x ULN, alanine aminotransferase (ALT) less than or equal to 2.5 x ULN 2.1.1.12 Amylase and lipase equal to, or less than, the institutional ULN. 2.1.1.13 Creatinine clearance greater than or equal to 40 ml/min (estimated or measured creatinine clearance) or serum creatinine less than or equal to 1.6 mg/dl 2.1.1.14 Random urine protein \< 20 mg/dL. If greater than or equal to 20 mg/dL then a 24-hour urine protein collection will be performed to accurately demonstrate that the 24-hour total is \<1000 mg, the level acceptable for enrollment on study 2.1.1.15 Absolute neutrophil count greater than or equal to 500/mm(3) 2.1.1.16 Platelet count greater than or equal to 50,000/ mm(3) 2.1.1.17 Ability to understand and sign an informed consent document. 2.1.1.18 Ability and willingness to follow the guidelines of the clinical protocol including visits to National Institute of Child Health and Human Development (NICHD) and National Cancer Institute (NCI), Bethesda, Maryland for treatment and follow up visits. 2.1.1.19 Because the effects of chemotherapy on the developing human fetus are potentially harmful, women of childbearing potential and men who participate in the study must agree to use adequate contraception (hormonal or barrier methods) before, during the study and for a period of 3 months after the last dose of chemotherapy. EXCLUSION CRITERIA 2.1.2.1 Patients with pheochromocytoma/paraganglioma tumors potentially curable by surgical excision alone as determined by the Principal Investigator in discussions with the surgical consultants 2.1.2.2 Patients who have large abdominal masses impinging on bowel or pulmonary masses with encroached vessels and a potential to bleed will be considered on case by case basis after careful consultation with multiple disciplines such as radiologists and surgeons with main intent being patient safety. 2.1.2.3 Unstable hypertension defined as a systolic blood pressure \>150 mm Hg or diastolic pressure \> 90 mmHg despite optimal medical management. 2.1.2.4 Untreated brain metastases (or local treatment of brain metastases within the last 6 months) due to the poor prognosis of these patients and difficulty ascertaining the cause of neurologic adverse events. 2.1.2.5 Pregnancy, due to the possible adverse effects on the developing fetus. 2.1.2.6 Lactating women who are breast-feeding due to the possibility of transmitting axitinib to the child. 2.1.2.7 The presence of a second malignancy, other than squamous cell carcinoma of the skin or in situ cervical cancer because it will complicate the primary objective of the study. Cancer survivors who have been free of disease for at least two years can be enrolled in this study. 2.1.2.8 Patients with evidence of a bleeding diathesis 2.1.2.9 Patients must not have received prior therapy with a tyrosine kinase inhibitor (TKI). Prior TKI usage in pheochromocytoma affects the same pathway as axitinib. 2.1.2.10 Gastrointestinal abnormalities including: * Inability to take oral medications * Requirement for intravenous alimentation * Prior surgical procedure affecting absorption including total gastric resection * Treatment for active peptic ulcer disease in the past 6 months * Active gastrointestinal bleeding, unrelated to cancer, as evidenced by hematemesis, hematochezia or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy * Malabsorption syndrome 2.1.2.11 Current use or anticipated need for treatment with drugs that are known potent Cytochrome P450 3A4 (CYP3A4) inhibitors (i.e., grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, erythromycin, telithromycin, clarithromycin, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir, and delavirdine). 2.1.2.12 Current use or anticipated need for treatment with drugs that are known CYP3A4 or Cytochrome P450 1A2, (CYP1A2) inducers (i.e., carbamazepine, dexamethasone, felbamate, omeprazole, phenobarbital, phenytoin, amobarbital, nevirapine, primidone, rifabutin, rifampin, and St. John's wort). 2.1.2.13 Requirement of anticoagulant therapy with oral vitamin K antagonists. Low-dose anticoagulants for maintenance of patency of central venous access devices or prevention of deep venous thrombosis is allowed. Therapeutic use of low molecular weight heparin is allowed. 2.1.2.14 Active seizure disorder or evidence of brain metastases, spinal cord compression, or carcinomatous meningitis. 2.1.2.15 Any of the following within 12 months prior to study drug administration: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack and within 6 months before study drug administration for deep vein thrombosis or pulmonary embolism. 2.1.2.16 Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study