SNIPP study - A investigator initiated phase II study of sunitinib in patients with recurrent paraganglioma/pheochromocytoma

Paragangliomas are highly vascularized tumors that arise from the
parasympathetic system and the adrenal medulla (pheochromocytoma) and can
produce catecholamines. A subset of these tumors are characterized by
pseudohypoxia: in tumor cells survival strategies for hypoxic conditions are
activated resulting among others in production of vascular endothelial growth
factor (VEGF) which induces angiogenesis.
The primary treatment of paraganglioma/pheochromocytoma is surgical resection.
However, some are malignant and metastasize. The 5-year survival for patients
with metastatic paraganglioma is less than 50%. In case of metastatic disease
it is recommende to perform debulking surgery is 80-90 % of the tumor bulk can
be safely excised, however no survival benefit has been demonstrated.
Chemotherapy can induce tumor responses of short dureation at the cost of
significant toxicity and is not routine practice in the Netherlands for
paraganglioma. Treatment with radioactive MIBG is offered to patients in the
Netherlands but it is not widely available and neither the optimal dose and
schedule as the influence on prognosis has been determined. Sunitinib is a
multi targeted tyrosine kinase inhibitor, blocking amogst others the VEGF
pathway. Sunitinib is standard first line treatment for patients with
metastatic renal cell carcinoma which is also characterized by pseudo-hypoxia.
Tumor response on sunitinib have been desrcinbed in patients with advanced and
metastatic paraganglioma.

To investigate if sunitinib has clinical significant activity in patients with
metastatic/recurrent paraganglioma/pheochromocytoma.

Non-randomized, non-blinded phase II study of sunitinib in patients with
advanced or metastatic recurrent paraganglioma or pheochromocytoma.

Sunitinib 50 mg will be administered orrally daily for 4 weeks out of every 6
weeks.

Patients can experience side effects of sunitinib, the most frequent are:
hypertension, fatigue, gastroinestinal symptoms and skin discoloration.
Patients have to visit the outpatient clinic once every 6 weeks, then blood
will be drawn and urinalaysis will be performed. After every 2 cycles response
will be assessed with a CT scan. Patients will be given a a blood pressure
device and will be asked to measure and write down their blood pressure weekly
during the first cycle and once every 2 weeks thereafter. Patients have to
write down intake of study mediation in a diary.
For patients who consent to a tumor biopsy, this will be performed after 2
treatment cycles. Patients who do not want a biopsy can participate to the
study.