Validation of a Multi-Genetic Test for the Diagnosis of Indeterminate Thyroid Nodules (CT-DS)

October 29, 2017 updated by: Hernán González

A clinical trial is proposed, to clinically validate the diagnostic performance of a new genetic test developed in Chile. It will determine the nature of thyroid nodules that have been informed as indeterminate by cytology through a fine needle aspiration (FNA).

The Genetic Classifier for Indeterminate Thyroid Nodules is a quantitative gene expression test, that combines the results for a panel of 10 biomarkers (CXCR3, CCR3, CXCl10, CK19, TIMP1, CLDN1, CAR, XB130, HO-1 and CCR7), to generate a single number score. It is indicated on patients with a thyroid nodule informed by cytology as indeterminate (Bethesda III and IV, according to The Bethesda System for Reporting Thyroid Cytopathology). This test would be used by taking a sample with a fine needle aspiration (FNA) and thus, being able to predict, with high accuracy, benign nodules that do not require surgery.

Study Overview

Status

Completed

Conditions

Detailed Description

Problem/Necessity: Throughout the world, each year, hundreds of thousands of patients undergo an unnecessary diagnostic surgery of the thyroid. This occurs in patients that have a FNA informed as indeterminate (which correspond to 15-20% of all FNA), due to have a risk of malignancy ranging from 15 to 25%. So, 75% of the indeterminate nodules are unnecessarily operated, which makes it essential to have a diagnostic tool that allows us to identify those patients with benign thyroid nodules and thus, avoid surgery.

Solution: We have developed a test that, through the analysis of the expression of 10 genes by PCR on real time in FNA samples, integrated by an algorithm, rules out the presence of cancer with a Negative Predictive Value (NPV) of 96% and Specificity of 81%.

Benefit/Justification: The high NPV will allow the clinician to recommend observation as an alternative to surgery. The 6% of false negatives is clinically accepted due to, cytology on its own, has 5% of false negatives. On the other hand, the 75% of specificity will allow to avoid surgery on 75% of the benign cases, which makes the test cost-effective.

State of Progress: The test has completed the phase of prototype development and analytical validation. The next stage is the clinical validation and it corresponds to the study proposed on this protocol.

Hypothesis: Our genetic test rules out the presence of cancer with a NPV higher that 94% and Specificity higher than 75% on indeterminate nodule samples.

Proposed study: A multi-centric (9 sites) clinical trial will be developed in Chile, with statistical power to determine the sensitivity and clinical specificity, negative and positive predictive values, likelihood ratios and confidence intervals.

Method: Patients that have a FNA indicated by their treating physician, due to they have an indeterminate nodule that requires to be determined if it is benign or malignant, will be invited to participate on this trial. After the informed consent is signed, a FNA sample will be obtained for cytology and for molecular study. Obtaining the sample for the molecular study will be part of the same procedure. A maximum of 4000 samples must be enrolled. Approximately 300 will fulfill all of the requirements to complete the study, which include: having a confirmed indeterminate cytology, be sent to surgery (gold standard), and have a proper mRNA sample. Throughout the study, the treating physician will not modify his conduct at any time and the decisions will be based on the clinical information that is regularly used.

Timeline/Monitoring: The study recruitment phase is expected to last an approximate of 28 months (24 months of enrollment, and 4 months of follow up as a minimum time to obtain the result for the surgical biopsy). However, this timeline might be extended while waiting for the 300 indeterminate samples to end study. There will be a principal investigator on each site, guided by a hired CRO, will guard the correct execution of the trial.

Study Type

Observational

Enrollment (Actual)

3100

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

  • Chile
      • Santiago, Chile
        • Hospital Clinico de la Universidad de Chile
    • Region Metropolitana
      • Santiago, Region Metropolitana, Chile
        • Clínica Alemana de Santiago
      • Santiago, Region Metropolitana, Chile
        • Centro de Diagnóstico Plaza Italia
      • Santiago, Region Metropolitana, Chile
        • Hospital Clinico de la Pontificia Universidad Catolica de Chile
    • Región Metropolitana
      • Santiago, Región Metropolitana, Chile
        • Clinica San Carlos de Apoquindo
      • Santiago, Región Metropolitana, Chile
        • Clinica Santa Maria
      • Santiago, Región Metropolitana, Chile
        • Fundacion Arturo Lopez Perez
      • Santiago, Región Metropolitana, Chile
        • Hospital del Salvador
      • Santiago, Región Metropolitana, Chile
        • Hospital San Juan de Dios

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

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

This study will be conducted on a patient population that has, according to their treating physicians, the clinical indication of FNA due to the presence of a thyroid nodule. Enough patients will be enrolled to obtain a maximum of 3600 to 4000 FNA. Patients will not be exposed to additional risks, beyond those that may occur as a result of the procedure of Fine Needle Aspiration. Patients that participate on this study, will be exposed to the (minimum) risks associated to the thyroid tissue sample technique by fine needle aspiration.

Description

Inclusion Criteria:

Patient ≥ 18 years old, male or female Patent with a thyroid nodule ≥ 8.0 mm of diameter measured by ultrasound. Patient with indication of thyroid fine needle aspiration (FNA). Patient with no record of spontaneous bleeding. Patient in condition to understand and sign the ICF.

Exclusion Criteria:

  1. Patient < 18 years old, male or female.
  2. Patient with an ultrasound diagnosis of thyroid nodule < 8.0 mm.
  3. Patient with record of spontaneous bleeding.
  4. Patient with current symptoms of bleeding.
  5. Patient in no condition of understanding and signing the ICF.

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Verify the sensitivity, specificity, NPV, PPV.
Time Frame: 30 months
Sensitivity: True Positives Specificity: True Negatives NPV: Ability to predict Benign PPV: Ability to predict Malignant
30 months

Collaborators and Investigators

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

Sponsor

Hernán González

Investigators

  • Study Director: Hernán E González, MD, Pontificia Universidad Catolica de Chile

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

August 8, 2015

Primary Completion (Actual)

August 30, 2017

Study Completion (Actual)

August 30, 2017

Study Registration Dates

First Submitted

February 17, 2017

First Submitted That Met QC Criteria

February 17, 2017

First Posted (Actual)

February 23, 2017

Study Record Updates

Last Update Posted (Actual)

October 31, 2017

Last Update Submitted That Met QC Criteria

October 29, 2017

Last Verified

October 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 14-463

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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