Trial Information

Longitudinal Assessment and Natural History Study of Children and Young Adults With Medullary Thyroid Carcinoma

Background:

- Medullary Thyroid Carcinoma (MTC) is a calcitonin producing tumor arising from the
parafollicular C cells of thyroid. In children and young adults, MTC is usually seen in
association with Multiple Endocrine Neoplasia (MEN) 2A and 2B, which are rare cancer
syndromes resulting from germline mutations of Rearranged during Transfection (RET)
proto-oncogene. MTC develops in virtually all patients with MEN 2, and is the leading
cause of death in these patients. Patients with MEN 2 may have other characteristic
manifestations such as pheochromocytoma and hyperparathyroidism in MEN 2A and
pheochromocytoma, ganglioneuromatosis, and skeletal deformities in MEN 2B.

- Complete surgical resection is the only current curative treatment for MTC, and the
tumor is unresponsive to standard chemotherapy and conventional doses of radiation
therapy. However, more than half the patients present with advanced or metastatic
disease and cannot be cured surgically. Novel agents are currently under investigation
for treatment of MTC, and vandetanib, an oral RET and receptor tyrosine kinase (RTK)
inhibitor was recently approved by the FDA for adults with advanced or metastatic MTC.
Vandetanib also has activity in children with hereditary MTC.

- However, complete responses to RTKs have not been observed, and some patients develop
resistance to the treatment with RET and RTK inhibitors or have primary refractory
disease. The natural history of MTC, particularly in patients with MEN 2, the
molecular pathways involved in tumorigenesis, and the development of resistance to
targeted therapies are not well understood.

Objectives:

-The overall objective of this longitudinal study is to develop a better understanding of
the biology and natural history of MTC, particularly in children and young adults with MEN
2A and 2B, as well as study non-tumor manifestations of MEN 2. This will hopefully allow for
developing more effective treatment interventions for tumor and non-tumor related
manifestations, and more sensitive endpoints in clinical trials.

Eligibility:

- Patients less than or equal to 25 years of age, must have histologically or
cytologically confirmed MTC, confirmed by the Laboratory of Pathology, NCI

- Participants may be undergoing standard care or receiving treatment on a clinical trial
while participating in this study.

Design:

This study will allow for longitudinal evaluations of MTC and non-tumor related
manifestations of MEN 2A and 2B in children and young adults. Evaluations will consist of
the following (summarized):

1. Clinical and radiological evaluations every 6 - 12 months

2. Detailed pathologic and molecular analysis of tumor specimens will be performed,
including immunohistochemistry (IHC), comparative genomic hybridization (CGH), and
genome sequencing.