Ignite Creation Date:
2024-05-06 @ 10:36 AM
Last Modification Date:
2024-10-26 @ 12:33 PM
Study NCT ID:
NCT03309631
Status:
UNKNOWN
Last Update Posted:
2017-10-26
First Post:
2017-10-01
Brief Title:
Clinical Validation of ThyroidPrint A Gene Expression Signature for Diagnosis of Indeterminate Thyroid Nodules
Sponsor:
Pontificia Universidad Catolica de Chile
Organization:
Pontificia Universidad Catolica de Chile
Study Overview
Official Title:
Clinical Validation of ThyroidPrint A Gene Expression Signature for Diagnosis of Indeterminate Thyroid Nodules
Status:
UNKNOWN
Status Verified Date:
2017-10
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
A clinical trial is proposed to clinically validate in a US population the diagnostic performance of a new genetic test ThyroidPrint 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 test that determines the expression of a panel of 10 biomarkers CXCR3 CCR3 CXCl10 CK19 TIMP1 CLDN1 CAR XB130 HO-1 and CCR7 Gene expression data is analyzed through an algorithm that generates a composite score that predicts the risk of malignancy Its intended use is for patients with thyroid cytology as indeterminate Bethesda III and IV according to The Bethesda System for Reporting Thyroid Cytopathology This test uses a fine needle aspiration FNA sample
Detailed Description:
Thyroid nodules are a very frequent condition reaching up to 30-40 of the adult population Although most thyroid nodules have little clinical significance in many cases a fine needle aspirate FNA biopsy will be performed to determine its nature In 70 of cases a FNA will be reported as benign and in 10 of cases as cancer However the remaining 20 of cases the thyroid nodule will be reported as indeterminate The latter patients have a risk of malignancy ranging from 15 to 25 and in most cases the patient will undergo thyroid lobectomy or total thyroidectomy to determine the final pathology resulting in an unacceptable number of unnecessary surgeries This has a major health impact including surgical risks and permanent hormonal supplementation as well as unwarranted health costs estimated at 16 billion USD Therefore there is a need for diagnostic tools in order to improve the diagnostic accuracy of the FNA and avoidance of the high rate of unnecessary surgeries
GeneproDx has developed a gene expression signature to improve the diagnostic accuracy of FNA biopsy of thyroid nodules reported as indeterminate The ThyroidPrint diagnostic measures the expression of 10 genes in a FNA sample It combines the results of the 10 biomarkers using a proprietary algorithm to predict benign thyroid nodules This assay is classified as multi-analyte algorithm assays MAAA
The biomarkers consist of multiplex TaqMan gene expression assays run on Qiagens Rotor-Gene Q MDx RT-PCR IVD Platform instrument which is a FDA cleared instrument The following 10 genes comprise the biomarker panel CXCR3 CCR3 CXCL10 CK19 TIMP1 CLDN1 CAR XB130 HO-1 and CCR7 Each gene run in a multiplex configuration with two reference genes Each assay is performed with Research Use Only RUO kits and reagents on a FDA cleared instrument
ThyroidPrint has been developed using two different cohorts of samples a training set and a testing set Using linear discriminant analysis the training set identified the final biomarker panel including CXCR3 CCR3 CXCL10 CK19 TIMP1 CLDN1 CAR XB130 HO-1 and CCR7 In brief the biomarkers have the following significance CCR3 and CCR7 are chemokine receptors that are highly expressed in papillary thyroid cancer tumor cells CXCR3 is also a chemokine receptor and along with its receptor CXCL10 are detected in thyroid autoimmune disease CAR is a G-couple receptor and has been shown to be involved in cancer and has decreased expression in parathyroid adenoma CK19 is a keratin and has been used in thyroid tumors to recognize papillary carcinomas CLDN1 is a structural protein and has been shown to be differentially expressed in tumors compared to normal tissue and has increased mRNA levels in papillary thyroid carcinoma XB130 is also a structural protein and its expression has been demonstrated in papillary thyroid carcinoma TIMP1 is a protease inhibitor with mRNA levels increased in advanced stages of thyroid carcinoma HO- 1 is an oxygenase and its expression has correlates with tumor aggressiveness in thyroid cancer In the final classifier the expression of each gene was weighted based on its individual relative classifying ability The cutoff score was chosen in the ROC curve generated in the training set based on a minimum Sensitivity of 92 to guarantee a high Negative Predictive Value 95 This cutoff score offered a Specificity of 83An independent testing set of samples reproduced the diagnostic performance observed in the training set and showed consistent results in FNA samples The assay has proven to accurately predict benign nodules in thyroid FNA samples with a Negative Predictive Value of 96 and Specificity of 83 in both cohorts The definitive validation of an MAAA requires a final validation set which analyzes samples that will be used in the routine clinical setting in this case indeterminate thyroid nodules samples In addition in order to show clinical validity the validation set must be performed as a statistically powered multi-institutional trial to assure that the data is applicable to a broad population spectrum and has appropriate confidence intervals A first statistically powered multi-institutional trial is currently underway in Chile to prove Clinical Validity This trial includes 8 sites and will recruit approximately 3000 FNA to be completed by December 2017
GeneproDx has developed a gene expression signature to improve the diagnostic accuracy of FNA biopsy of thyroid nodules reported as indeterminate The ThyroidPrint diagnostic measures the expression of 10 genes in a FNA sample It combines the results of the 10 biomarkers using a proprietary algorithm to predict benign thyroid nodules This assay is classified as multi-analyte algorithm assays MAAA
The biomarkers consist of multiplex TaqMan gene expression assays run on Qiagens Rotor-Gene Q MDx RT-PCR IVD Platform instrument which is a FDA cleared instrument The following 10 genes comprise the biomarker panel CXCR3 CCR3 CXCL10 CK19 TIMP1 CLDN1 CAR XB130 HO-1 and CCR7 Each gene run in a multiplex configuration with two reference genes Each assay is performed with Research Use Only RUO kits and reagents on a FDA cleared instrument
ThyroidPrint has been developed using two different cohorts of samples a training set and a testing set Using linear discriminant analysis the training set identified the final biomarker panel including CXCR3 CCR3 CXCL10 CK19 TIMP1 CLDN1 CAR XB130 HO-1 and CCR7 In brief the biomarkers have the following significance CCR3 and CCR7 are chemokine receptors that are highly expressed in papillary thyroid cancer tumor cells CXCR3 is also a chemokine receptor and along with its receptor CXCL10 are detected in thyroid autoimmune disease CAR is a G-couple receptor and has been shown to be involved in cancer and has decreased expression in parathyroid adenoma CK19 is a keratin and has been used in thyroid tumors to recognize papillary carcinomas CLDN1 is a structural protein and has been shown to be differentially expressed in tumors compared to normal tissue and has increased mRNA levels in papillary thyroid carcinoma XB130 is also a structural protein and its expression has been demonstrated in papillary thyroid carcinoma TIMP1 is a protease inhibitor with mRNA levels increased in advanced stages of thyroid carcinoma HO- 1 is an oxygenase and its expression has correlates with tumor aggressiveness in thyroid cancer In the final classifier the expression of each gene was weighted based on its individual relative classifying ability The cutoff score was chosen in the ROC curve generated in the training set based on a minimum Sensitivity of 92 to guarantee a high Negative Predictive Value 95 This cutoff score offered a Specificity of 83An independent testing set of samples reproduced the diagnostic performance observed in the training set and showed consistent results in FNA samples The assay has proven to accurately predict benign nodules in thyroid FNA samples with a Negative Predictive Value of 96 and Specificity of 83 in both cohorts The definitive validation of an MAAA requires a final validation set which analyzes samples that will be used in the routine clinical setting in this case indeterminate thyroid nodules samples In addition in order to show clinical validity the validation set must be performed as a statistically powered multi-institutional trial to assure that the data is applicable to a broad population spectrum and has appropriate confidence intervals A first statistically powered multi-institutional trial is currently underway in Chile to prove Clinical Validity This trial includes 8 sites and will recruit approximately 3000 FNA to be completed by December 2017
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None