A Retrospective Study to Determine the Incidence of NTRK Fusions. NTRK Study (NTRK)

A Study to Determine the Incidence of NTRK Fusions in Subjects With Locally Advanced/Unresectable or Metastatic Solid Tumors With NTRK Fusions and Related Treatment Outcomes.

This retrospective study has a primary objective to estimate the incidence of NTRK gene fusion depending on the histological diagnosis.

Study Overview

• Status: Completed
• Conditions: Metastatic Solid Tumors
• Intervention / Treatment: Other: No intervention (this is a retrospective cohort study)

Detailed Description

This retrospective study has a primary objective to estimate the incidence of NTRK gene fusion depending on the histological diagnosis. The tropomyosin receptor kinase (Trk) receptor family comprises 3 transmembrane proteins referred to as Trk A, B and C (TrkA, TrkB and TrkC) receptors that are encoded by the NTRK1, NTRK2 and NTRK3 genes, respectively. These receptor tyrosine kinases are expressed in human neuronal tissue and play an essential role in the physiology of development and function of the nervous system through activation by neurotrophins. Gene fusions involving NTRK genes lead to transcription of chimeric Trk proteins with constitutively activated or overexpressed kinase function conferring oncogenic potential. These genetic abnormalities have recently emerged as targets for cancer therapy, because novel compounds have been developed that are selective inhibitors of the constitutively active rearranged proteins. Developments in this field are being aided by next generation sequencing methods as tools for unbiased gene fusions discovery. However, the incidence of NTRK aberrations in solid tumors is unknown as well as the natural history of NTRK-rearranged tumors This study will provide better knowledge of NTRK gene fusion incidence to allow recommendations for pathological diagnosis.

Subjects who are tested positive by Immunohistochemistry (IHC : Pan-Trk IHC testing with mAb EPR17341) will be the subject of molecular assays such as next-generation sequencing (Archer Dx fusion assay) of tumor material [parrafin embedded material]), so that tumor harboring NTRK1, NTRK2 or NTRK3 gene fusions, is identified properly.

• Study Type: Observational
• Enrollment (Actual): 3820

Contacts and Locations

Study Locations

• France
  • Aquitaine
    • Bordeaux, Aquitaine, France, 33000
      • Institut Bergonie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The cohort will included both adult and pediatric patients with metastatic solid tumors, who have received at least one systemic anti-cancer therapy for advanced disease and for which there is available both outcome information and tumor material.

Description

Inclusion Criteria:

• Age ≥ 1 month.
• Subject has/had a histologically or cytologically confirmed diagnosis of solid tumor including but not exclusively: soft tissue sarcoma, BRAF wild type melanoma, KRAS wild-type colorectal cancer, central nervous system, EGFR-wild type non-small cell lung cancer.
• Subject has locally advanced/unresectable or metastatic disease.
• Subject has received at least one systemic anti-cancer therapy for locally advanced/unresectable or metastatic disease for which there is available outcome information in terms of PFS, or the latter can be estimated based on the subject's records.
• Subject has tumor material available for immunoscreening (IHC for NTRK gene fusions).
• Written and voluntary informed consent understood, signed and dated, or a waiver of consent is granted according to French régulations.

Exclusion Criteria:

• Subjects who have not yet received or completed at least one systemic anti-cancer therapy for locally advanced/unresectable or metastatic cancer.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Subjects With Locally Advanced/Unresectable or Metastatic Solid Tumors	Other: No intervention (this is a retrospective cohort study); No intervention (this is a retrospective cohort study) aimed at describing tumour samples. No treatment/intervention is being tested.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Count of Participants With NRTK Fusions Among Participants Analyzed by NGS (Next-generation Sequencing).	A participant with NRTK fusion is defined as a participant with a tumor harboring NTRK1, NTRK2 or NTRK3 gene fusions, based on NGS (Next-generation sequencing methods). NGS (Next-generation sequencing methods) method: DNA and RNA were extracted from tumor tissue according to standard procedures. All samples had their RNA analyzed with Archer or full RNA sequencing to assess specific novel NTRK1, 2, and 3 rearrangements for the production of NTRK fusion transcripts. Alternatively, DNA was analyzed by using an hybrid-capture based NGS assay as previously described.	at baseline (i.e. at the time of tumor removal)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Count of Participants With NRTK Fusions Among Participants With With Positive Immunohistochemistry (IHC)	A participant with NRTK fusion is defined as a participant with a tumor harboring NTRK1, NTRK2 or NTRK3 gene fusions, based on Immunohistochemistry (IHC). Immunohistochemistry (IHC) mehtod : Pan-TRK: rabbit monoclonal antibody, clone C17F1, Cell signaling dilution 1/50°. Automate Benchmark: ULTRA Ventana, CC1 64', incubation 52', revelation kit Optiview	at baseline (i.e. at the time of tumor removal)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS) in Patients With NRTK Gene Fusion.	PFS is calculated using Kaplan-Meier method, in the population of patients with positive IHC results.	Two years after tumor removal

Collaborators and Investigators

• Sponsor: Institut Bergonié
• Collaborators: Bayer
• Investigators: Principal Investigator: Antoine ITALIANO, MD, PhD, a.italiano@bordeaux.unicancer.fr

Study record dates

Study Major Dates

• Study Start (Actual): December 23, 2015
• Primary Completion (Actual): December 31, 2022
• Study Completion (Actual): December 31, 2022

Study Registration Dates

• First Submitted: July 3, 2019
• First Submitted That Met QC Criteria: July 3, 2019
• First Posted (Actual): July 8, 2019

Study Record Updates

• Last Update Posted (Estimated): October 16, 2025
• Last Update Submitted That Met QC Criteria: September 26, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Metastatic; Solid tumor; NTRK
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Pathological Conditions, Signs and Symptoms; Neoplasm Metastasis
• Other Study ID Numbers: IB2015-NTRK; MR 0112040319 (Other Identifier: Insitut National des Données de Santé (INDS))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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