A Retro-/Prospective, Non-interventional, Cohort Study in Adult Patients With Locally Advanced or Metastatic Tumors With a Neurotrophic Tyrosine Receptor Kinase (NTRK) Gene Fusion, Treated With Larotrectinib

Metastatic Cancer Clinical Trial

— LAROTRACKING  

Official title:

LAROTRACKING - A Retro-/Prospective, Non-interventional, Cohort Study in Adult Patients With Locally Advanced or Metastatic Tumors With a Neurotrophic Tyrosine Receptor Kinase (NTRK) Gene Fusion, Treated With Larotrectinib

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04814667
• Other study ID #: LAROTRACKING
• Status: Active, not recruiting
• Start date: February 23, 2021
• Est. completion date: June 2025

Study information

• Verified date: July 2023
• Source: Centre Leon Berard
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Larotrectinib, a selective TRK inhibitor has showed marked and durable antitumor activity in patients with NTRK gene-fusion-positive tumors regardless of the tumor type, gene partner and patient's age. Because of this and the lack of alternative therapy in this rare but severe disease, the French National Agency for Medicines and Health Products Safety (ANSM) granted in April 2019, a "cohort" Temporary Authorization for Use (ATU) in the indication:"Larotrectinib is indicated as monotherapy for the treatment of adult and paediatric patients from one month, with locally advanced or metastatic solid tumours with a Neurotrophic Tyrosine Receptor Kinase (NTRK) fusion, refractory to standard treatments or in the absence of appropriate therapeutic alternative." Despite the potential benefit of identifying these fusions, the clinicopathologic features of NTRK fusion-positive tumors which are treated with Larotrectinib, are not well characterized. This study will provide information about the diagnosis and management of patients with locally advanced or metastatic NTRK fusion cancer treated with Larotrectinib under real-world treatment conditions in France, and describes the dosing patterns, safety and effectiveness of this agent.

Description:

Tropomyosin receptor kinases (TRK) are a family of tyrosine kinases that bind neurotrophins, a family of growth factors important to the formation and function of the nervous system. In cancer, the neurotrophic tyrosine kinase receptor (NTRK)1, NTRK2 and NTRK3 genes, which encode for the TRKA, TRKB and TRKC proteins, respectively, are subject to gene-arrangements that lead to kinase domain expression and constitutive downstream pathway activation. In preclinical models, NTRK gene fusions have transformative oncogenic potential, and they appear to be widely distributed across histologically diverse adult and pediatric cancers. Hence, these genetic abnormalities, observed in both children and adults, have recently emerged as targets for cancer therapy.

Larotrectinib, a selective TRK inhibitor has showed marked and durable antitumor activity in patients with NTRK gene-fusion-positive tumors regardless of the tumor type, gene partner and patient's age.

Because of this and the lack of alternative therapy in this rare but severe disease, the French National Agency for Medicines and Health Products Safety (ANSM) granted in April 2019, a "cohort" Temporary Authorization for Use (ATU) in the indication:

"Larotrectinib is indicated as monotherapy for the treatment of adult and paediatric patients from one month, with locally advanced or metastatic solid tumours with a Neurotrophic Tyrosine Receptor Kinase (NTRK) fusion, refractory to standard treatments or in the absence of appropriate therapeutic alternative." Despite the potential benefit of identifying these fusions, the clinicopathologic features of NTRK fusion-positive tumors which are treated with Larotrectinib, are not well characterized.

This study will provide information about the diagnosis and management of patients with locally advanced or metastatic NTRK fusion cancer treated with Larotrectinib under real-world treatment conditions in France, and describes the dosing patterns, safety and effectiveness of this agent.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 27
• Est. completion date: June 2025
• Est. primary completion date: November 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years and older

Eligibility

Inclusion Criteria:

• Adult male or female patients

• Histological confirmed diagnosis of advanced/metastatic solid tumor type.

• Patients previously, currently or to be treated with Larotrectinib within the ATU/post-ATU period. Patient must be > 25 years-old at time of larotrectinib start.

• Patients not opposed to collection of personal clinical data

Related Conditions & MeSH terms

• Locally Advanced Solid Tumor
• Metastatic Cancer
• Neoplasm Metastasis
• Neoplasms
• Solid Tumor, Adult

Locations

Country	Name	City	State
France	CHU Amiens	Amiens
France	Centre Georges Francois Leclerc	Dijon
France	Centre Leon Berard	Lyon
France	Chi Elbeuf Louviers	Saint-Aubin-lès-Elbeuf

Sponsors (2)

Lead Sponsor	Collaborator
Centre Leon Berard	Bayer

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical activity of larotrectinib	Best objective response rate (BORR) (Complete Response or Partial Response as per RECIST V1.1 assessed by investigators)	From the date of the first larotrectinib dose until the date of objectively documented progression or date of subsequent anti-cancer therapy, whichever came first, assessed up to 60 months.
Primary	Clinical activity of larotrectinib	Duration of response (DOR) (Best overall response of Complete Response or Partial Response as per RECIST V1.1)	From the start of Complete Response or Partial Response (whichever response came first) until the date of observed disease progression or death due to any cause, whichever came first, assessed up to 60 months.
Primary	Clinical activity of larotrectinib	Time to response (TTR)	From the start of larotrectinib treatment until the first evidence of Objective Response as per RECIST V1.1, assessed up to 60 months. Time to response will be calculated for responders only.
Primary	Clinical activity of larotrectinib	Progression-free survival (PFS)	From the start of Larotrectinib treatment until the date of first observed disease progression (radiological or clinical, whichever came first) or death due to any cause, whichever came first, assessed up to 60 months
Primary	Clinical activity of larotrectinib	Overall survival (OS)	From the start of larotrectinib treatment until the date of death, due to any reason, assessed up to 60 months. Patients alive or lost to follow-up at the time of analysis will be censored at their last date of follow-up.
Secondary	Clinicopathological features of patients with locally advanced or metastatic NTRK fusion cancer for whom a decision to treat with larotrectinib was made before enrolment.	Demographics data, significant or relevant medical history, cancer disease overview	Through study completion, an average of 60 months.
Secondary	Diagnosis strategy for detection of NTRK fusions in the investigational centers	Description of the diagnosis tests used for NTRK fusions	Through study completion, an average of 60 months.
Secondary	Treatment(s) received prior to and after larotrectinib.	Doses, duration, best tumor response and reasons for discontinuation	From the first dose of larotrectinib until the day of permanent discontinuation of larotrectinib (including death), assessed up to 60 months .
Secondary	Patterns of larotrectinib treatment	Dosing paramaters	From the start of larotrectinib treatment until the day of permanent discontinuation of larotrectinib (including death), assessed up to 60 months
Secondary	Safety of larotrectinib	Adverse events : Nature, frequency and severity of Adverse Events (AEs), Serious Adverse Events (SAEs) and Suspected Unexpected Serious Adverse Reactions (SUSARs) graded using Common Terminology Criteria for Adverse Events (CTCAE) V5.0.	Through study completion, an average of 60 months.
Secondary	Molecular characteristics of NTRK rearrangements	Gene name, type of alteration	Through study completion, an average of 60 months.