Dovitinib in Neuroendocrine Tumors

This investigator-initiated study is being conducted to evaluate whether the investigational
drug, Dovitinib, can shrink or slow the growth of cancer in patients with certain types of
neuroendocrine tumors (advanced malignant pheochromocytoma or paraganglioma). The primary
endpoint will be response rate (Complete + Partial Response) determined by RECIST v 1.1. 25
subjects will be enrolled on this study at the University of Pennsylvania.

Inclusion Criteria:

- Patients with advanced, metastatic, recurrent or unresectable paraganglioma or
pheochromocytoma. Pathology report or pathology slides (H&E) confirming histological
diagnosis must be available at the time of enrollment.

- Must have measurable disease by RECIST v1.1.

- ECOG performance status 0, 1, 2

- Age greater or equal to 18 years old

- Adequate laboratory results; negative pregnancy test (females of childbearing
potential)

- Patients who give a written informed consent obtained according to institutional
guidelines

Exclusion Criteria:

- Patients with known untreated brain metastases are excluded. Patients having a history
of brain metastasis that have been previously irradiated or resected greater than 3
months prior to enrollment and are clinically and radiographically stable will be
considered for enrollment.

- Patients with another primary malignancy within 3 years prior to starting study drug,
with the exception of adequately treated in-situ carcinoma of the uterine cervix, or
skin cancer (such as basal cell carcinoma, squamous cell carcinoma, or
non-melanomatous skin cancer)

- Patients who have received the last administration of an anticancer therapy including
chemotherapy, immunotherapy, hormonal therapy and monoclonal antibodies (but excluding
nitrosurea, mitomycin-C, targeted therapy and radiation) less than or equal to 4 weeks
prior to starting study drug, or who have not recovered from the side effects of such
therapy

- Patients who have received the last administration of nitrosurea or mitomycin-C less
than or equal to 6 weeks prior to starting study drug, or who have not recovered from
the side effects of such therapy

- Patients who have received bevacizumab, sunitinib, sorafenib, or pazopanib less than
or equal to 2 weeks prior to starting study drug, or who have not recovered (grade 1)
from the side effects of these therapies.

- Patients who have had radiotherapy less than or equal to 4 weeks prior to starting
study drug, or less than or equal to 2 weeks prior to starting study drug in the case
of localized radiotherapy (e.g. for analgesic purpose or for lytic lesions at risk of
fracture), or who have not recovered from radiotherapy toxicities

- Patients who have had therapeutic radiolabeled MIBG or other systemic radiolabeled
therapy less than or equal to 4 weeks prior to starting study drug,

- Patients who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or
intra-pelvic), open biopsy or significant traumatic injury less than or equal to 4
weeks prior to starting study drug, or patients who have had minor procedures,
percutaneous biopsies or placement of vascular access device 1 week prior to starting
study drug, or who have not recovered from side effects of such procedure or injury

- Patients with any of the following concurrent severe and/or uncontrolled medical
conditions which could compromise participation in the study (i.e. impaired cardiac
function or clinically significant cardiac diseases, etc).

- Pregnant or breastfeeding women or any subjects who refuse to use protocol required
contraception

- Patients unwilling or unable to comply with the protocol