Ignite Creation Date:
2025-12-25 @ 2:32 AM
Ignite Modification Date:
2025-12-30 @ 9:16 AM
Study NCT ID:
NCT02268734
Status:
COMPLETED
Last Update Posted:
2021-09-30
First Post:
2014-09-04
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Molecular Profile of Metastatic Sporadic Medullary Thyroid Cancer Patients and Correlation With Vandetanib
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITH_DNA', 'description': 'primary tumor and metastases tissue samples and other biological materials, including blood are collected'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'RETROSPECTIVE', 'observationalModel': 'CASE_ONLY'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 36}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2014-04', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2021-09', 'completionDateStruct': {'date': '2018-12', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2021-09-29', 'studyFirstSubmitDate': '2014-09-04', 'studyFirstSubmitQcDate': '2014-10-16', 'lastUpdatePostDateStruct': {'date': '2021-09-30', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2014-10-20', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2017-12', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Validation of a miRNA profile', 'timeFrame': '8 months', 'description': 'To validate the miRNA profile proposed by previous studies in sMTC in our series of metastatic sMTC'}, {'measure': 'Define any correlations between the miRNA profiles and RET, and H- and K-RAS mutations', 'timeFrame': '8 months', 'description': 'To assess whether there is any correlation between the miRNA profiles and RET, and H- and K-RAS mutations displayed by the same tumors'}, {'measure': 'Define a circulating miRNA profile', 'timeFrame': '8 months', 'description': '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'}, {'measure': 'Analyze any change in circulating miRNAs', 'timeFrame': '8 months', 'description': 'To analyze any change in circulating miRNAs profile according to the TKI treatment (vandetanib)'}, {'measure': 'Correlate circulating miRNA profile with the burden of disease', 'timeFrame': '8 months', 'description': 'To correlate circulating miRNA profile with the burden of disease and, possibly, with the genetic lesion of the primary tumors (RET and RAS mutations)'}, {'measure': 'Evaluate the correlation between the response to vandetanib and the patients molecular profile', 'timeFrame': '8 months', 'description': 'To evaluate the correlation between the response to vandetanib and the patients molecular profile including tissue miRNA, circulating miRNA and genetic lesion'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['Sporadic Medullary Thyroid Cancer Vandetanib miRNA'], 'conditions': ['Metastatic Sporadic Medullary Thyroid Cancer']}, 'descriptionModule': {'briefSummary': '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.\n\nCirculating 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.\n\nAim of this project is to seek non-invasive molecular markers potentially useful as prognostic tools for metastatic MTC patients.', 'detailedDescription': '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.\n\nVandetanib 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.\n\nNo 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.\n\nAim of this project is to seek non-invasive molecular markers potentially useful as prognostic tools for metastatic MTC patients.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': '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', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* diagnosis of sMTC surgically treated (total thyroidectomy)\n* locally relapsed and or metastatic sMTC\n* 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).\n\nExclusion Criteria:\n\n* Patients with severe infection, active clinical co-morbidities, or a history of any other malignancy have been excluded.'}, 'identificationModule': {'nctId': 'NCT02268734', 'briefTitle': 'Molecular Profile of Metastatic Sporadic Medullary Thyroid Cancer Patients and Correlation With Vandetanib', 'organization': {'class': 'OTHER', 'fullName': 'Fondazione IRCCS Istituto Nazionale dei Tumori, Milano'}, 'officialTitle': 'Molecular Profile of Metastatic Sporadic Medullary Thyroid Cancer (sMTC) Patients and Possible Correlation With Vandetanib Therapy', 'orgStudyIdInfo': {'id': '178/13'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'Sporadic Medullary Thyroid Cancer', 'description': 'Patients with diagnosis of locally relapsed and or metastatic sporadic MTC surgically treated (total thyroidectomy)'}]}, 'contactsLocationsModule': {'locations': [{'zip': '20133', 'city': 'Milan', 'country': 'Italy', 'facility': 'Fondazione IRCCS Istituto Nazionale dei Tumori, Milano', 'geoPoint': {'lat': 42.78235, 'lon': 12.59836}}], 'overallOfficials': [{'name': 'Laura Locati, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Fondazione IRCCS Istituto Nazionale dei Tumori, Milano'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Fondazione IRCCS Istituto Nazionale dei Tumori, Milano', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}