Clinical trial NCT05796258: Three-pronged Centralized Molecular Analysis to Optimize Detection of NTRK1,2,3 Fusions in Thyroid Cancer
Official title: A Multi-institutional Effort With a Three-pronged Centralized Molecular Analysis to Optimize Detection of NTRK1,2,3 Fusions in Thyroid Cancer
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Thyroid Cancer
Keywords: ntrk fusion
Lead sponsor: Regina Elena Cancer Institute
Sponsor class: OTHER
Collaborators: name: University of Roma La Sapienza
name: Bambino Gesù Hospital and Research Institute
First posted: 2023-04-03
Enrollment: 100
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients affected by advanced thyroid cancer (any histotype)

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).

Eligibility criteria: 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

Primary outcomes:
measure: Frequency of NTRK fusions in thyroid cancer
timeFrame: from 01-Jan-2022 to 31-Dec-2023
Secondary outcomes:
measure: Assesment of the ability of Immunohistochemistry to identify for NTRK fusion
timeFrame: from 01-Jan-2022 to 31-Dec-2023
measure: Assesment of the ability of real time PCR to identify for NTRK fusion
timeFrame: from 01-Jan-2022 to 31-Dec-2023
Other outcomes:
Locations:
city: Roma
country: Italy
facility: Regina Elena National Cancer Institute
Study officials:
affiliation: Regina Elena Cancer Institute
name: Marialuisa Appetecchia, Prof
role: PRINCIPAL_INVESTIGATOR
References: