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

Completed

• Conditions: Metastatic Solid Tumors
• Interventions: Other: Retrospective cohort

• Registration Number: NCT04010240
• Lead Sponsor: Institut Bergonié

Brief Summary

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

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.

Study Timeline

• Study Start: 2015-12-23
• Study First Submitted: 2019-07-03
• Study First Submitted QC: 2019-07-03
• Study First Posted: 2019-07-08
• Primary Completion: 2020-12-01
• Study Completion: 2020-12-01
• Status Verified: 2022-08
• Last Update Submitted: 2022-08-24
• Last Update Posted: 2022-08-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 3820

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Retrospective cohort	Retrospective cohort	For eligible subject, tumor material will be tested by immunohistochemistry (Pan-Trk ICH testing with mAb EPR17341).

Primary Outcome Measures

Name	Time	Method
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

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

Trial Locations

Locations (1)

Institut Bergonié; 🇫🇷 Bordeaux, Aquitaine, France