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

Completed

• Conditions: Thyroid Cancer

• Registration Number: NCT05796258
• Lead Sponsor: Regina Elena Cancer Institute

Brief 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).

Detailed 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).

Study Timeline

• Study Start: 2021-07-26
• Study First Submitted: 2023-03-16
• Study First Submitted QC: 2023-03-31
• Study First Posted: 2023-04-03
• Primary Completion: 2023-12-31
• Status Verified: 2024-12
• Study Completion: 2024-12-04
• Last Update Submitted: 2024-12-04
• Last Update Posted: 2024-12-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 100

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Frequency of NTRK fusions in thyroid cancer	from 01-Jan-2022 to 31-Dec-2023	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

Secondary Outcome Measures

Name	Time	Method
Assesment of the ability of real time PCR to identify for NTRK fusion	from 01-Jan-2022 to 31-Dec-2023	To assess the ability of real time PCR to detect NTRK fusion on histological sample (using NGS as comparator)
Assesment of the ability of Immunohistochemistry to identify for NTRK fusion	from 01-Jan-2022 to 31-Dec-2023	To assess the ability of Immunohistochemistry to detect NTRK fusion on histological sample (using NGS as comparator)

Trial Locations

Locations (1)

Regina Elena National Cancer Institute; 🇮🇹 Roma, Italy