Background:~Most treatments for malignant pheochromocytomas/paragangliomas (PHEO/PGL) are palliative and multidisciplinary. Chemotherapy using the combination of cyclophosphamide, vincristine, and dacarbazine has been successfully utilized in the management of rapidly progressive metastatic PHEO, with more than 50% complete or partial tumor response and more than 70% complete or partial biochemical response.~Vascular endothelial growth factor (VEGF) expression and evidence of angiogenesis has been found in many PHEO/PGL, so it is plausible that interfering with VEGF signaling may result in anti-tumor activity in patients with PHEO/PGL.~Axitinib (AG-013736) is an oral, potent and selective inhibitor of vascular endothelial growth factor (VEGF) receptors 1, 2, and 3. Pre-clinical data suggests that the anti-tumor activity of axitinib may result from its anti-angiogenic activity and that this is reversible when treatment is discontinued.~Given the known clinical safety and efficacy of axitinib, an assessment of its activity in PHEO/PGL and its impact on the VEGF pathway in PHEO/PGL could provide valuable information.~Objectives:~Determine the response rate of metastatic PHEO/PGL to axitinib (AG-013736).~Determine the progression-free survival of metastatic PHEO/PGL treated with axitinib (AG-013736).~Explore the relationship of potential biological markers of axitinib activity with clinical outcomes.~Perform pharmacogenomics analyses of drug metabolism and transport proteins through germline deoxyribonucleic acid (DNA) examination.~Eligibility:~Adults with a confirmed pathologic diagnosis of PHEO/PGL by the Laboratory of Pathology, National Cancer Institute (NCI)~Biochemical evidence of PHEO/PGL~Imaging confirmation of metastatic, locally advanced or unresectable disease.~Measurable disease at presentation~Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2~Patients must not have received prior therapy with a tyrosine kinase (TK) inhibitor~Design:~Phase II, open label, non-randomized trial~Patients with metastatic pheochromocytoma/paraganglioma will receive axitinib (AG-013736 twice a day (BID)) in eight-week cycles~Patients will be evaluated for response every twelve weeks (+/- 1 week) using Response Evaluation Criteria in Solid Tumors (RECIST) criteria~Approximately 12 to 37 patients will be needed to achieve the objectives of the trial
Background:~Most treatments for malignant pheochromocytomas/paragangliomas (PHEO/PGL) are palliative and multidisciplinary. Chemotherapy using the combination of cyclophosphamide, vincristine, and dacarbazine has been successfully utilized in the management of rapidly progressive metastatic PHEO, with more than 50% complete or partial tumor response and more than 70% complete or partial biochemical response.~Vascular endothelial growth factor (VEGF) expression and evidence of angiogenesis has been found in many PHEO/PGL, so it is plausible that interfering with VEGF signaling may result in anti-tumor activity in patients with PHEO/PGL.~Axitinib (AG-013736) is an oral, potent and selective inhibitor of vascular endothelial growth factor (VEGF) receptors 1, 2, and 3. Pre-clinical data suggests that the anti-tumor activity of axitinib may result from its anti-angiogenic activity and that this is reversible when treatment is discontinued.~Given the known clinical safety and efficacy of axitinib, an assessment of its activity in PHEO/PGL and its impact on the VEGF pathway in PHEO/PGL could provide valuable information.~Objectives:~Determine the response rate of metastatic PHEO/PGL to axitinib (AG-013736).~Determine the progression-free survival of metastatic PHEO/PGL treated with axitinib (AG-013736).~Explore the relationship of potential biological markers of axitinib activity with clinical outcomes.~Perform pharmacogenomics analyses of drug metabolism and transport proteins through germline deoxyribonucleic acid (DNA) examination.~Eligibility:~Adults with a confirmed pathologic diagnosis of PHEO/PGL by the Laboratory of Pathology, National Cancer Institute (NCI)~Biochemical evidence of PHEO/PGL~Imaging confirmation of metastatic, locally advanced or unresectable disease.~Measurable disease at presentation~Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2~Patients must not have received prior therapy with a tyrosine kinase (TK) inhibitor~Design:~Phase II, open label, non-randomized trial~Patients with metastatic pheochromocytoma/paraganglioma will receive axitinib (AG-013736 twice a day (BID)) in eight-week cycles~Patients will be evaluated for response every eight weeks using Response Evaluation Criteria in Solid Tumors (RECIST) criteria~Tumor biopsies are not mandatory but every attempt will be made to obtain these from patients prior to starting axitinib and again 20 - 30 days after treatment has begun.~Approximately 12 to 37 patients will be needed to achieve the objectives of the trial