Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02268734 |
| Other study ID # |
178/13 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
April 2014 |
| Est. completion date |
December 2018 |
Study information
| Verified date |
September 2021 |
| Source |
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Vandetanib has been approved for patients with unresectable and/or metastatic medullary
thyroid cancer (MTC) by the Food and Drug Administration, by the European Medicines Agency
and, very recently, it has been licensed also by the Italian Regulatory Agency (AIFA) for the
use in Italy. Vandetanib is an orally tyrosine kinase inhibitor (TKI) of vascular endothelial
growth factor receptor (VEGFR), epidermal growth factor receptor (EGFR), and RET signaling.
Circulating microRNAs levels could be influenced by the treatment procedures and we
hypothesize that a TKI therapy could influence the levels of circulating miRNAs as well.
Aim of this project is to seek non-invasive molecular markers potentially useful as
prognostic tools for metastatic MTC patients.
Description:
Medullary thyroid cancer (MTC) is considered worldwide a rare cancer. It derives from the
parafolicular C-cells representing about 5-10% of all thyroid cancer. MTC is diagnosed as
sporadic form (sMTC) in most of the patients, although in 20-30% of cases it could be
hereditary and transmitted as an autosomal-dominant trait due to the germline mutations of
the RET proto-oncogene. RET tyrosine kinase receptor is involved in the regulation of
differentiation, proliferation, survival and cell motility processes through several
intracellular signalling pathways, including MAPK and PI3K/AKT/mTOR pathways.
Vandetanib has been approved for patients with unresectable and/or metastatic MTC by the Food
and Drug Administration, by the European Medicines Agency and, very recently, it has been
licensed also by the Italian Regulatory Agency (AIFA) for the use in Italy. Vandetanib is an
orally tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor receptor
(VEGFR), epidermal growth factor receptor (EGFR), and RET signaling. In a randomized phase
III trial, response rate to vandetanib ranged from 31% to 55% with a predicted median
progression-free survival (PFS) of 30.5 months while data on overall survival were still not
available at the time of publication. These results suggest that approximately half of the
patients could benefit from this compound whose activity is in every case limited in the
time. Activity of vandetanib seems to be influenced by several factors, including RET
mutational status and tumor genetic heterogeneity (clonal versus non-clonal RET mutation
distribution). Recent analyses of circulating miRNAs in tumor patients have suggested that
miRNA signatures may be useful as diagnostic/prognostic/predictive as well as pharmacodynamic
markers for several tumor types.
No clinical neither biological data are currently available to identify which patients could
really get a benefit from a TKI. In other words, some metastatic patients could suffer from
an indolent disease, not requiring a TKI upfront and up to date, we are still not able to
identify this selected group of patients Circulating miRNAs levels could be influenced by the
treatment procedures, as it has been described in lung cancer where miR-21 and miR-24
resulted significantly lower in the post-operative period respect to the pre-operative one in
paired samples. We hypothesize that a TKI therapy could influence the levels of circulating
miRNAs as well.
Aim of this project is to seek non-invasive molecular markers potentially useful as
prognostic tools for metastatic MTC patients.
