Study Of Sunitinib In Patients With Recurrent Paraganglioma/Pheochromocytoma (SNIPP)

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of malignant paraganglioma or pheochromocytoma and either evidence of metastases or unresectability.
• Evidence of recent disease progression (radiological, biochemical, symptomatic).
• Measurable disease defined as that which can be measured in at least one dimension with a minimum size of 10 mm by CT scan.
• ECOG 0-2.
• Life expectancy of greater than 24 weeks.
• Age > 18 years.
• Patients must have normal organ and marrow function.
• Patients must have PT/INR/PTT within 1.2 X the upper limit
• Patients may have had prior radiation therapy. A minimum of 28 days must have elapsed between the end of radiotherapy and registration onto the study.
• Previous Surgery: Previous major surgery is permitted provided that it has been at least 28 days prior to patient registration
• Laboratory Requirements Parameter Limit granulocytes (AGC) > 1.5 x 109/L platelets > 100 x 109/L bilirubin < 1.5XULN AST and ALT < 2.5 x ULN Amylase <1.5XULN Lipase <1.5XULN Calcium < 3 mmol/L creatinine < 2.0XULN

Exclusion Criteria:

• History of other malignancies.
• Patients with known brain metastases.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to sunitinib.
• Patients receiving concurrent treatment with other anti-cancer therapy given for paraganglioma or pheochromocytoma or other therapy or other investigational anticancer agents.
• Patients who have received prior treatment with any other antiangiogenic agent or multi-targeted tyrosine kinase inhibitors are ineligible.
• Patients with any of the following cardiovascular findings are to be excluded:
• QTc prolongation or other significant ECG abnormalities.
• Current or history of Class III or IV heart failure as defined by the NYHA functional classification system
• Patients with prior anthracycline exposure, previous central thoracic radiation that included heart in radiation port, or a history of NYHA Class II cardiac function.
• Poorly controlled hypertension
• Myocardial infarction, cardiac arrhythmia, stable/unstable angina, symptomatic congestive heart failure, or coronary/peripheral artery bypass graft or stenting within 12 months prior to study entry
• History of venous thrombosis or pulmonary embolism in the past 3 months
• History of cerebrovascular accident (CVA) or transient ischemic attack within 12 months prior to study entry
• Patients who require use of therapeutic doses of coumarin-derivative anticoagulants such as warfarin
• Patients with bowel obstruction or any condition that impairs their ability to swallow and retain sunitinib tablets.
• Use of agents with proarrhythmic potential is not permitted during the study.
• Must be able to stop prohibited selected CYP3A4 inhibitors/inducers prior to starting sunitinib
• Patients with pre-existing hypothyroidism prior to enrolment are ineligible unless they are euthyroid on medication.
• Pregnant or lactating women, positive pregnancy test, women of childbearing potential who do not agree to use adequate contraception prior to study entry and for the duration of study participation.
• Known HIV-positive patients on combination antiretroviral therapy
• Greater than +1 proteinuria on urinary dipstick if also >1g urinary protein/24hrs