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

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

Detailed Description
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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.

Official Title
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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.

Conditions
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Metastatic Solid Tumors

Intervention / Treatment
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* Other: Retrospective cohort


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 1 Month

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Retrospective cohort<br>For eligible subject, tumor material will be tested by immunohistochemistry (Pan-Trk ICH testing with mAb EPR17341). | Other: Retrospective cohort<br>* Tumor material tested positive will be analyzed by next-generation sequencing to identify NTRK1, NTRK2 or NTRK3 gene fusions.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of NTRK fusions in subjects with locally advanced/unresectable or metastatic solid tumors. |  | Retrospective analysis between January 2019 and December 2020 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment outcome in terms of objective response rate. | ORR will be defined as the proportion of patients with objective response (complete or partial response) during the first-line anti-cancer therapy. | Retrospective analysis between January 2019 and December 2020 | 
| Treatment outcome in terms of progression-free survival. | PFS will be defined as the delay from the date of onset of first-line anti-cancer therapy to the date of progression. | Retrospective analysis between January 2019 and December 2020 | 
| Treatment outcome in terms of overall survival | OS will be defined as the delay from the date of start first-line anti-cancer therapy to the date of death (whatever the cause). | Retrospective analysis between January 2019 and December 2020 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Solid tumor, Metastatic, NTRK