Three-pronged Centralized Molecular Analysis to Optimize Detection of NTRK1,2,3 Fusions in Thyroid Cancer

Thyroid Cancer Clinical Trial

— NTRK  

Official title:

A Multi-institutional Effort With a Three-pronged Centralized Molecular Analysis to Optimize Detection of NTRK1,2,3 Fusions in Thyroid Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05796258
• Other study ID #: RS1445/20(2421)
• Status: Active, not recruiting
• Start date: July 26, 2021
• Est. completion date: June 30, 2024

Study information

• Verified date: April 2024
• Source: Regina Elena Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This multi-center study aims at NTRK fusion testing of all patients with advanced thyroid cancer (any histotype and regardless of stage). The primary objective of this study is to assess the frequency of NTRK fusions in thyroid cancer. The secondary objective of this study is to develop an effective tool (testing) strategy for the detection of NTRK fusions in thyroid tumors, comparing the diagnostic tecniques available (IHC, real-time PCR and NGS).

Description:

Thyroid cancer is the most common neoplasm of the endocrine system. Most thyroid carcinomas originate from the follicular epithelium and are distinguished in differentiated forms (DTC): papillary (PTC) and follicular (FTC) carcinomas. Both have a favorable prognosis and account for approximately 80% and 10% of all thyroid neoplasms, respectively. The undifferentiated form represented by the anaplastic thyroid carcinoma (ATC) is less frequent (about 2%) and represents one of the most aggressive human tumors with a survival that rarely exceeds 6-12 months. Medullary thyroid carcinoma (MTC), deriving from parafollicular C cells, is relatively rare (approximately 5%) and is associated with an intermediate prognosis between differentiated and poorly differentiated forms.

As to the prevalence of NTRK lesions, many authoritative papers and reviews claim very high (up to 75%) NTRK fusion frequencies, particularly in the common PTC. However, an extensive PubMed analysis back to year 1990 does not provide convincing support for this claim.Several techniques for NTRK fusion diagnosis exist, including pan-Trk IHC, FISH, reverse transcription PCR, DNA-based next-generation sequencing (NGS), and RNA-based NGS. Each of these assays has unique features, advantages, and limitations, and familiarity with these assays is critical to appropriately screen for NTRK fusions.

The aim of this study is to determine the frequency of NTRK fusions in advanced thyroid cancer patients and to compare the diagnostic tecniques available (IHC, real-time PCR and NGS).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 100
• Est. completion date: June 30, 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Diagnosis of advanced thyroid cancer (any histotype)

• Informed consent.

Exclusion Criteria:

• Patients with thyroid neoplasms without appropriate material for subsequent immunohistochemical and molecular studies;

• Patients with non-advanced thyroid cancer

Related Conditions & MeSH terms

• Thyroid Cancer
• Thyroid Diseases
• Thyroid Neoplasms

Intervention

Diagnostic Test:
• NTRK fusion assessment
To evaluate NTRK fusion presence by MCG, Immunohistochemistry or NGS

Locations

Country	Name	City	State
Italy	Regina Elena National Cancer Institute	Roma

Sponsors (3)

Lead Sponsor	Collaborator
Regina Elena Cancer Institute	Bambino Gesù Hospital and Research Institute, University of Roma La Sapienza

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of NTRK fusions in thyroid cancer	To assess the frequency of NTRK fusions in histological sample of tumors by patients affected by thyroid cancer, assessed as the number of tumor harboring NTRK fusion on the total of tumor analized	from 01-Jan-2022 to 31-Dec-2023
Secondary	Assesment of the ability of Immunohistochemistry to identify for NTRK fusion	To assess the ability of Immunohistochemistry to detect NTRK fusion on histological sample (using NGS as comparator)	from 01-Jan-2022 to 31-Dec-2023
Secondary	Assesment of the ability of real time PCR to identify for NTRK fusion	To assess the ability of real time PCR to detect NTRK fusion on histological sample (using NGS as comparator)	from 01-Jan-2022 to 31-Dec-2023