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

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ClinicalTrials.gov Identifier: NCT02268734
Recruitment Status : Unknown
Verified October 2014 by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano.
Recruitment status was:  Recruiting
First Posted : October 20, 2014
Last Update Posted : October 20, 2014
Sponsor:
Information provided by (Responsible Party):
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Brief 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.


Condition or disease
Metastatic Sporadic Medullary Thyroid Cancer

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
Estimated Enrollment : 25 participants
Observational Model: Case-Only
Time Perspective: Retrospective
Official Title: Molecular Profile of Metastatic Sporadic Medullary Thyroid Cancer (sMTC) Patients and Possible Correlation With Vandetanib Therapy
Study Start Date : April 2014
Estimated Primary Completion Date : December 2014
Estimated Study Completion Date : December 2014


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



Primary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. Analyze any change in circulating miRNAs [ Time Frame: 8 months ]
    To analyze any change in circulating miRNAs profile according to the TKI treatment (vandetanib)

  5. 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)

  6. 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


Biospecimen Retention:   Samples With DNA
primary tumor and metastases tissue samples and other biological materials, including blood are collected


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02268734


Contacts
Contact: Laura Locati, MD +39 022390 ext 2765 laura.locati@istitutotumori.mi.it

Locations
Italy
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano Recruiting
Milano, Italy, 20133
Contact: Laura Locati, MD    +39 022390 ext 2765    laura.locati@istitutotumori.mi.it   
Principal Investigator: Laura Locati, MD         
Sponsors and Collaborators
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Investigators
Principal Investigator: Laura Locati, MD Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Responsible Party: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
ClinicalTrials.gov Identifier: NCT02268734     History of Changes
Other Study ID Numbers: 178/13
First Posted: October 20, 2014    Key Record Dates
Last Update Posted: October 20, 2014
Last Verified: October 2014

Keywords provided by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano:
Sporadic Medullary Thyroid Cancer Vandetanib miRNA

Additional relevant MeSH terms:
Thyroid Diseases
Thyroid Neoplasms
Carcinoma, Neuroendocrine
Endocrine System Diseases
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue