Clinical trial NCT04814667: 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
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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Solid Tumor, Adult
Locally Advanced Solid Tumor
Metastatic Cancer
Keywords: NTRK gene fusion
Larotrectinib
Neurotrophic Tyrosine Receptor Kinase gene fusion
NTRK rearrangements
Lead sponsor: Centre Leon Berard
Sponsor class: OTHER
Collaborators: name: Bayer
First posted: 2021-03-24
Enrollment: 26
Sex: ALL
Minimum age (years): 25
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult patients with locally advanced or metastatic tumors with a Neurotrophic Tyrosine Receptor Kinase (NTRK) gene fusion, treated with Larotrectinib

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Clinical activity of larotrectinib
timeFrame: 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.
measure: Clinical activity of larotrectinib
timeFrame: 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.
measure: Clinical activity of larotrectinib
timeFrame: From the start of larotrectinib treatment until the first evidence of Objective Response according to RECIST V1.1 classification i.e assessed by investigators), assessed up to 60 months. Time to response will be calculated for responders only.
measure: Clinical activity of larotrectinib
timeFrame: 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
measure: Clinical activity of larotrectinib
timeFrame: 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 outcomes:
measure: Clinicopathological features of patients with locally advanced or metastatic NTRK fusion cancer for whom a decision to treat with larotrectinib was made before enrolment.
timeFrame: Through study completion, an average of 60 months.
measure: Diagnosis strategy for detection of NTRK fusions in the investigational centers
timeFrame: Through study completion, an average of 60 months.
measure: Treatment(s) received prior to and after larotrectinib.
timeFrame: From the first dose of larotrectinib until the day of permanent discontinuation of larotrectinib (including death), assessed up to 60 months .
measure: Patterns of larotrectinib treatment
timeFrame: From the start of larotrectinib treatment until the day of permanent discontinuation of larotrectinib (including death), assessed up to 60 months
measure: Safety of larotrectinib
timeFrame: Through study completion, an average of 60 months.
measure: Molecular characteristics of NTRK rearrangements
timeFrame: Through study completion, an average of 60 months.
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU Amiens
city: Dijon
country: France
facility: Centre Georges Francois Leclerc
city: Lyon
country: France
facility: Centre Leon Berard
city: Saint-Aubin-lès-Elbeuf
country: France
facility: Chi Elbeuf Louviers
Study officials:
affiliation: Centre Leon Berard
name: Armelle DUFRESNE
role: PRINCIPAL_INVESTIGATOR
References: