A Investigator Initiated Phase II Study Of Sunitinib In Patients With Recurrent Paraganglioma/Pheochromocytoma
- 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
- 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
- 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
- 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
- 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