Indeterminate Thyroid Cytology Clinical Trial
Official title:
Validation of a Multi-Genetic Test for the Diagnosis of Indeterminate Thyroid Nodules
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.
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.
;
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Recruiting |
NCT03309631 -
Clinical Validation of ThyroidPrint: A Gene Expression Signature for Diagnosis of Indeterminate Thyroid Nodules
|
N/A |