Locally Advanced Solid Tumor, Metastatic Cancer, Solid Tumor, Adult
Conditions
Keywords
NTRK gene fusion, Larotrectinib, Neurotrophic Tyrosine Receptor Kinase gene fusion, NTRK rearrangements
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.
Interventions
None listed
Sponsors
Bayer
Centre Leon Berard
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
25 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical activity of larotrectinib | 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. | Best objective response rate (BORR) (Complete Response or Partial Response according to RECIST V1.1 classification i.e assessed by investigators) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Diagnosis strategy for detection of NTRK fusions in the investigational centers | Through study completion, an average of 60 months. | Description of the diagnosis tests used for NTRK fusions |
| Treatment(s) received prior to and after larotrectinib. | From the first dose of larotrectinib until the day of permanent discontinuation of larotrectinib (including death), assessed up to 60 months . | Doses, duration, best tumor response and reasons for discontinuation |
| Clinicopathological features of patients with locally advanced or metastatic NTRK fusion cancer for whom a decision to treat with larotrectinib was made before enrolment. | Through study completion, an average of 60 months. | Demographics data, significant or relevant medical history, cancer disease overview |
| Safety of larotrectinib | Through study completion, an average of 60 months. | 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. |
| Molecular characteristics of NTRK rearrangements | Through study completion, an average of 60 months. | Gene name, type of alteration |
| Patterns of larotrectinib treatment | From the start of larotrectinib treatment until the day of permanent discontinuation of larotrectinib (including death), assessed up to 60 months | Dosing paramaters |
Countries
France
Outcome results
None listed