Metastatic Sporadic Medullary Thyroid CancerNCT02268734
Molecular Profile of Metastatic Sporadic Medullary Thyroid Cancer Patients and Correlation With Vandetanib
An observational study of Metastatic Sporadic Medullary Thyroid Cancer, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano at 1 site in Italy.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Sporadic Medullary Thyroid Cancer
- How many people
- 36 participants
- Where
- 1 siteItaly
- Study dates
- Apr 2014to Dec 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Who may be able to join
- 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).
Who cannot join
- Patients with severe infection, active clinical co-morbidities, or a history of any other malignancy have been excluded.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Keywords
- Sporadic Medullary Thyroid Cancer Vandetanib miRNA
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Sporadic Medullary Thyroid Cancer | Patients with diagnosis of locally relapsed and or metastatic sporadic MTC surgically treated (total thyroidectomy) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Validation of a miRNA profile
To validate the miRNA profile proposed by previous studies in sMTC in our series of metastatic sMTC
Measured: 8 months
Define any correlations between the miRNA profiles and RET, and H- and K-RAS mutations
To assess whether there is any correlation between the miRNA profiles and RET, and H- and K-RAS mutations displayed by the same tumors
Measured: 8 months
Define a circulating miRNA profile
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
Measured: 8 months
Analyze any change in circulating miRNAs
To analyze any change in circulating miRNAs profile according to the TKI treatment (vandetanib)
Measured: 8 months
Correlate circulating miRNA profile with the burden of disease
To correlate circulating miRNA profile with the burden of disease and, possibly, with the genetic lesion of the primary tumors (RET and RAS mutations)
Measured: 8 months
Evaluate the correlation between the response to vandetanib and the patients molecular profile
To evaluate the correlation between the response to vandetanib and the patients molecular profile including tissue miRNA, circulating miRNA and genetic lesion
Measured: 8 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2014 (estimated)
- Study startApr 2014
- Primary completionDec 2017
- Study completionDec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Sporadic Medullary Thyroid CancerStudies of the same condition, open and under way.
- More trials run by Fondazione IRCCS Istituto Nazionale dei Tumori, MilanoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Retrospective
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Laura Locati, MD, Principal investigator, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02268734
- Sponsor's protocol ID
- 178/13
- Status last verified
- Sep 2021
- First submitted
- 4 Sep 2014
- Last updated
- 30 Sep 2021
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Molecular Profile of Metastatic Sporadic Medullary Thyroid Cancer (sMTC) Patients and Possible Correlation With Vandetanib Therapy
- ClinicalTrials.gov ID
- NCT02268734
- Acronym / sponsor ID
- 178/13
- Keywords
- Sporadic Medullary Thyroid Cancer Vandetanib miRNA
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Fondazione IRCCS Istituto Nazionale dei Tumori, MilanoUniversity, hospital or other
- Study start
- Apr 2014 (actual)
- Primary completion
- Dec 2017 (actual)
- Study completion
- Dec 2018 (actual)
- First posted
- 20 Oct 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Case only
- Time perspective
- Retrospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sporadic Medullary Thyroid Cancer | – | –Patients with diagnosis of locally relapsed and or metastatic sporadic MTC surgically treated (total thyroidectomy) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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
Key inclusion criteria (3 listed)
- 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).
Key exclusion criteria (1 listed)
- Patients with severe infection, active clinical co-morbidities, or a history of any other malignancy have been excluded.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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
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
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
Analyze any change in circulating miRNAs
Time frame: 8 months
To analyze any change in circulating miRNAs profile according to the TKI treatment (vandetanib)
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)
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2021.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Laura Locati, MD principal investigator
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Metastatic Sporadic Medullary Thyroid Cancer, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Validation of a miRNA profile (time frame: 8 months). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Sep 2021.