Molecular Profile of Metastatic Sporadic Medullary Thyroid Cancer Patients and Correlation With Vandetanib

September 29, 2021 updated by: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Molecular Profile of Metastatic Sporadic Medullary Thyroid Cancer (sMTC) Patients and Possible Correlation With Vandetanib Therapy

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.

Study Overview

Status

Completed

Conditions

Detailed 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.

Study Type

Observational

Enrollment (Actual)

36

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Milano, Italy, 20133
        • Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Petient with a diagnosis of sporadic locally relapsed and or metastatic medullary thyroid cancer surgically treated (total thyroidectomy) who adheres to a voluntary program of donation of own biological materials to a biorepository

Description

Inclusion Criteria:

  • diagnosis of sMTC surgically treated (total thyroidectomy)
  • locally relapsed and or metastatic sMTC
  • metastatic MTC never treated with TKI before (valid for subjects treated with vandetanib only, in whom we will investigate the variation of circulating miRNA profile before and after vandetanib administration).

Exclusion Criteria:

  • Patients with severe infection, active clinical co-morbidities, or a history of any other malignancy have been excluded.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Sporadic Medullary Thyroid Cancer
Patients with diagnosis of locally relapsed and or metastatic sporadic MTC surgically treated (total thyroidectomy)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Validation of a miRNA profile
Time Frame: 8 months
To validate the miRNA profile proposed by previous studies in sMTC in our series of metastatic sMTC
8 months
Define any correlations between the miRNA profiles and RET, and H- and K-RAS mutations
Time Frame: 8 months
To assess whether there is any correlation between the miRNA profiles and RET, and H- and K-RAS mutations displayed by the same tumors
8 months
Define a circulating miRNA profile
Time Frame: 8 months
To define a circulating miRNA profile in our series of metastatic sMTC and to assess whether miRNAs over-expressed in tumors are also present in plasma samples of the same sMTC patients
8 months
Analyze any change in circulating miRNAs
Time Frame: 8 months
To analyze any change in circulating miRNAs profile according to the TKI treatment (vandetanib)
8 months
Correlate circulating miRNA profile with the burden of disease
Time Frame: 8 months
To correlate circulating miRNA profile with the burden of disease and, possibly, with the genetic lesion of the primary tumors (RET and RAS mutations)
8 months
Evaluate the correlation between the response to vandetanib and the patients molecular profile
Time Frame: 8 months
To evaluate the correlation between the response to vandetanib and the patients molecular profile including tissue miRNA, circulating miRNA and genetic lesion
8 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Investigators

  • Principal Investigator: Laura Locati, MD, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

April 1, 2014

Primary Completion (ACTUAL)

December 1, 2017

Study Completion (ACTUAL)

December 1, 2018

Study Registration Dates

First Submitted

September 4, 2014

First Submitted That Met QC Criteria

October 16, 2014

First Posted (ESTIMATE)

October 20, 2014

Study Record Updates

Last Update Posted (ACTUAL)

September 30, 2021

Last Update Submitted That Met QC Criteria

September 29, 2021

Last Verified

September 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 178/13

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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