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.