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

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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Thyroid Cancer
• Intervention / Treatment: Diagnostic test: NTRK fusion assessment

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 Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Marialuisa Appetecchia, Prof; Phone Number: 00390652666026; Email: marialuisa.appetecchia@ifo.it

Study Locations

• Italy
  • Roma, Italy, 00144
    • Regina Elena National Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients affected by advanced thyroid cancer (any histotype)

Description

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 Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Collaborators and Investigators

• Sponsor: Regina Elena Cancer Institute
• Collaborators: University of Roma La Sapienza; Bambino Gesù Hospital and Research Institute
• Investigators: Principal Investigator: Marialuisa Appetecchia, Prof, Regina Elena Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): July 26, 2021
• Primary Completion (Actual): December 31, 2023
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: March 16, 2023
• First Submitted That Met QC Criteria: March 31, 2023
• First Posted (Actual): April 3, 2023

Study Record Updates

• Last Update Posted (Actual): April 10, 2024
• Last Update Submitted That Met QC Criteria: April 9, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: ntrk fusion
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Endocrine System Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Thyroid Diseases; Thyroid Neoplasms
• Other Study ID Numbers: RS1445/20(2421)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Raw data will be published in open access databases
• IPD Sharing Time Frame: After study end
• IPD Sharing Access Criteria: open access
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No