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Indeterminate Thyroid CytologyCT-DSNCT03061318

Validation of a Multi-Genetic Test for the Diagnosis of Indeterminate Thyroid Nodules

An observational study of Indeterminate Thyroid Cytology, run by Hernán González at 9 sites in Chile.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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). Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for
Indeterminate Thyroid Cytology
How many people
3,100 participants
Where
9 sitesChile
Study dates
8 Aug 2015to 30 Aug 2017
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
  • Healthy volunteers accepted
  • Adult, Older adult

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.

Who may be able to join

  • 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.

Who cannot join

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

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

Chile9 sites
  • Centro de Diagnóstico Plaza Italia

    Santiago, Santiago Metropolitan

  • Clínica Alemana de Santiago

    Santiago, Santiago Metropolitan

  • Clínica San Carlos de Apoquindo

    Santiago, Santiago Metropolitan

  • Clínica Santa María

    Santiago, Santiago Metropolitan

  • Fundación Arturo López Pérez

    Santiago, Santiago Metropolitan

  • Hospital Clínico de la Pontificia Universidad Católica de Chile

    Santiago, Santiago Metropolitan

  • Hospital del Salvador

    Santiago, Santiago Metropolitan

  • Hospital San Juan de Dios

    Santiago, Santiago Metropolitan

  • Hospital Clínico de la Universidad de Chile

    Santiago

Other trials in Chile

About this study

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.

Read the 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.

Keywords
Fine Needle Aspiration, Genetic Classifier

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Verify the sensitivity, specificity, NPV, PPV.

    Sensitivity: True Positives Specificity: True Negatives NPV: Ability to predict Benign PPV: Ability to predict Malignant

    Measured: 30 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Feb 2017
  2. Study start8 Aug 2015
  3. Primary completion30 Aug 2017
  4. Study completion30 Aug 2017

Resources

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
Cohort
Time perspective
Prospective
Enrolment
3,100 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03061318
Sponsor's protocol ID
14-463
Acronym
CT-DS
Status last verified
Oct 2017
First submitted
17 Feb 2017
Last updated
31 Oct 2017
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Sipos JA, Mazzaferri EL. Thyroid cancer epidemiology and prognostic variables. Clin Oncol (R Coll Radiol). 2010 Aug;22(6):395-404. doi: 10.1016/j.clon.2010.05.004. Epub 2010 Jun 3.

    PubMed 20627675
  • Pellegriti G, Frasca F, Regalbuto C, Squatrito S, Vigneri R. Worldwide increasing incidence of thyroid cancer: update on epidemiology and risk factors. J Cancer Epidemiol. 2013;2013:965212. doi: 10.1155/2013/965212. Epub 2013 May 7.

    PubMed 23737785
  • Davies L, Welch HG. Current thyroid cancer trends in the United States. JAMA Otolaryngol Head Neck Surg. 2014 Apr;140(4):317-22. doi: 10.1001/jamaoto.2014.1.

    PubMed 24557566
  • Sosa JA, Hanna JW, Robinson KA, Lanman RB. Increases in thyroid nodule fine-needle aspirations, operations, and diagnoses of thyroid cancer in the United States. Surgery. 2013 Dec;154(6):1420-6; discussion 1426-7. doi: 10.1016/j.surg.2013.07.006. Epub 2013 Oct 2.

    PubMed 24094448
  • Bongiovanni M, Spitale A, Faquin WC, Mazzucchelli L, Baloch ZW. The Bethesda System for Reporting Thyroid Cytopathology: a meta-analysis. Acta Cytol. 2012;56(4):333-9. doi: 10.1159/000339959. Epub 2012 Jul 25.

    PubMed 22846422
  • Wang CC, Friedman L, Kennedy GC, Wang H, Kebebew E, Steward DL, Zeiger MA, Westra WH, Wang Y, Khanafshar E, Fellegara G, Rosai J, Livolsi V, Lanman RB. A large multicenter correlation study of thyroid nodule cytopathology and histopathology. Thyroid. 2011 Mar;21(3):243-51. doi: 10.1089/thy.2010.0243. Epub 2010 Dec 29.

    PubMed 21190442
  • Hodak SP, Rosenthal DS; American Thyroid Association Clinical Affairs Committee. Information for clinicians: commercially available molecular diagnosis testing in the evaluation of thyroid nodule fine-needle aspiration specimens. Thyroid. 2013 Feb;23(2):131-4. doi: 10.1089/thy.2012.0320. Epub 2012 Nov 27.

    PubMed 22984796
  • Nikiforova MN, Wald AI, Roy S, Durso MB, Nikiforov YE. Targeted next-generation sequencing panel (ThyroSeq) for detection of mutations in thyroid cancer. J Clin Endocrinol Metab. 2013 Nov;98(11):E1852-60. doi: 10.1210/jc.2013-2292. Epub 2013 Aug 26.

    PubMed 23979959
  • Nikiforov YE, Ohori NP, Hodak SP, Carty SE, LeBeau SO, Ferris RL, Yip L, Seethala RR, Tublin ME, Stang MT, Coyne C, Johnson JT, Stewart AF, Nikiforova MN. Impact of mutational testing on the diagnosis and management of patients with cytologically indeterminate thyroid nodules: a prospective analysis of 1056 FNA samples. J Clin Endocrinol Metab. 2011 Nov;96(11):3390-7. doi: 10.1210/jc.2011-1469. Epub 2011 Aug 31.

    PubMed 21880806
  • Alexander EK, Kennedy GC, Baloch ZW, Cibas ES, Chudova D, Diggans J, Friedman L, Kloos RT, LiVolsi VA, Mandel SJ, Raab SS, Rosai J, Steward DL, Walsh PS, Wilde JI, Zeiger MA, Lanman RB, Haugen BR. Preoperative diagnosis of benign thyroid nodules with indeterminate cytology. N Engl J Med. 2012 Aug 23;367(8):705-15. doi: 10.1056/NEJMoa1203208. Epub 2012 Jun 25.

    PubMed 22731672
  • Ali SZ, Fish SA, Lanman R, Randolph GW, Sosa JA. Use of the afirma(R) gene expression classifier for preoperative identification of benign thyroid nodules with indeterminate fine needle aspiration cytopathology. PLoS Curr. 2013 Feb 11;5:ecurrents.eogt.e557cbb5c7e4f66568ce582a373057e7. doi: 10.1371/currents.eogt.e557cbb5c7e4f66568ce582a373057e7.

    PubMed 23437421
  • Najafzadeh M, Marra CA, Lynd LD, Wiseman SM. Cost-effectiveness of using a molecular diagnostic test to improve preoperative diagnosis of thyroid cancer. Value Health. 2012 Dec;15(8):1005-13. doi: 10.1016/j.jval.2012.06.017. Epub 2012 Sep 25.

    PubMed 23244801
  • Bustin SA, Benes V, Garson JA, Hellemans J, Huggett J, Kubista M, Mueller R, Nolan T, Pfaffl MW, Shipley GL, Vandesompele J, Wittwer CT. The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments. Clin Chem. 2009 Apr;55(4):611-22. doi: 10.1373/clinchem.2008.112797. Epub 2009 Feb 26.

    PubMed 19246619
  • Pfaffl MW. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 2001 May 1;29(9):e45. doi: 10.1093/nar/29.9.e45.

    PubMed 11328886
  • Vergara IA, Norambuena T, Ferrada E, Slater AW, Melo F. StAR: a simple tool for the statistical comparison of ROC curves. BMC Bioinformatics. 2008 Jun 5;9:265. doi: 10.1186/1471-2105-9-265.

    PubMed 18534022

Questions about this trial

What is this clinical trial studying?

An observational study of Indeterminate Thyroid Cytology, run by Hernán González at 9 sites in Chile.

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 1 inclusion and 5 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 31 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in Chile. 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?

Verify the sensitivity, specificity, NPV, PPV. (time frame: 30 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03061318, which also lists 17 linked publications.

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 31 Oct 2017.

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