Registry for Molecular Testing, Treatment and Outcome of Patients With Solid Tumors Harboring a NTRK Gene Fusion

Study Overview
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Brief Summary
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The objective of this registry is to analyze treatment reality and outcome of patients with locally advanced or metastatic solid tumors harboring a fusion of NTRK1, NTRK2 or NTRK3

Detailed Description
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The REALTRK registry will provide data on treatment reality of patients with locally advanced or metastatic solid tumors harboring NTRK1, NTRK2 or NTRK3 gene fusions, thereby generating real world evidence. It will identify factors that influence treatment decisions after receiving the diagnosis of a NTRK (Neurotrophic Tyrosine Receptor Kinase) fusion-positive cancer. All treatment lines administered before and after the molecular diagnosis of a NTRK fusion-positive cancer, irrespective of the type of antineoplastic treatment, will be documented. Data will be assessed at least 36 months per patient (i.e. until 36 months after inclusion of the last patient in the study). This approach will allow a description of TRK fusion protein-targeted therapies and other therapy strategies regarding effectiveness and disease-related symptomology within the limitations of non-randomized studies in terms of comparative analyses. Intra-individual and inter-individual comparisons (for the latter, provided that a sufficient number of patients with a NTRK fusion-positive cancer are not treated with a TRK inhibitor) could be performed. The associated biomarker profiling module of the REALTRK registry will aim to set up a decentralized biobank for future research on molecular alterations.

Official Title
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Registry for Molecular Testing, Treatment and Outcome of Patients With Locally Advanced or Metastatic Solid Tumors Harboring a Fusion of NTRK1, NTRK2 or NTRK3

Conditions
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NTRK Family Gene Mutation

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Locally advanced or metastatic solid tumor with a documented NTRK gene fusion, based on a validated assay (according to current ESMO recommendations), or the provision of tumor material for central retesting Molecular pathology or molecular diagnostics report with details on NTRK gene fusion testing must be available Aged ≥ 18 years Signed and dated informed consent form (ICF) (only if patient is alive at time of data entry into the project; not applicable for inclusion of deceased patients' data) Exclusion Criteria: Treatment with a TRK inhibitor prior to Sept 19th, 2019 (Germany) or May 28th, 2020 (Switzerland) Participation in a clinical trial with a TRK inhibitor before or at enrolment (liv-ing patients) or before inclusion (deceased patients) Deceased patients who have explicitly contradicted further use of data

Ages Eligible for Study
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Minimum Age: 18 Years

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 |
| --- | --- |
| IC before start of any treatment<br>Informed consent (IC) before start of any treatment after diagnosis of NTRK fusion-positive cancer. All data after diagnosis of NTRK fusion-positive cancer are collected prospectively. | |
| IC after start of any treatment<br>IC after start of any treatment after diagnosis of NTRK fusion-positive cancer. Data after study inclusion are collected prospectively and retrospectively. | |
| Deceased patients<br>Patients deceased prior to study inclusion (no IC required). All data are collected retrospectively. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate | Proportion of patients with CR or PR as best response | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient and disease characteristics | Descriptive summary of demographics, patient and disease characteristics | 36 months | 
| Test methods used for diagnosis of a NTRK fusion-positive cancer | Description of test methods used for diagnosis of a NTRK fusion-positive cancer and results thereof | Day 1 | 
| Physician-reported factors affecting decision to test for NTRK fusion and treatment decision | Description of physician-reported factors affecting decision to test for NTRK fusion and treatment decision making after diagnosis of NTRK gene fusion | Day 1 | 
| Treatment reality after diagnosis of NTRK gene fusion | Description of all treatment lines given to the patient after diagnosis of NTRK gene fusion including: Type of treatment (Systemic TRK inhibitor treatments or Non-TRK inhibitor treatments), treatment duration, dosing, treatment modifications and reasons thereof, reasons for end of treatment. | 36 months | 
| Safety of TRK inhibitor treatments | Treatment-emergent AEs (i.e., AEs which occurred during a specific TRK inhibitor treatment and in the respective survival FU) will be calculated per patient (absolute and relative frequencies) and case-based (absolute frequencies). The occurrence of any (S)AE will be displayed overall and per CTCAE grade. Adverse drug reactions (ADRs) and AESIs will be displayed accordingly. Incidence of AEs (MedDRA Preferred Term (PT) by System Organ Class (SOC)) will be calculated accordingly for each type of AE/ADR. | 36 months | 
| Physician-reported evaluation of TRK inhibitor therapy | Description of physician-reported evaluation of TRK inhibitor therapy | Day 1 | 
| Disease-related symptoms | Description of courses of disease-related symptoms (weight loss, ECOG) after diagnosis of NTRK gene fusion (Only for patients of inclusion group I) | 36 months | 
| Disease control rate | Proportion of patients with CR, PR or SD as best response | 36 months | 
| Time to Response | Time from start of treatment to the first objective tumor response (e.g., tumor shrinkage of ≥30%) observed for patients who achieved a CR or PR | 36 months | 
| Duration of Response | Time from documentation of tumor response to disease progression or death from any cause | 36 months | 
| Progression-free survival | Time from start of treatment until disease progression or death | 36 months | 
| Overall Survival | Time from start of treatment until death of any cause | 36 months | 
| PFS ratio | ratio of PFS of the first treatment line with a TRK inhibitor to time to progression (TTP) in the preceding treatment line without a TRK inhibitor | 36 months | 
| Event-free survival | Time from start of treatment until PD or death | 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NTRK, NTRK-fusion, Neurotrophic Tyrosine Receptor Kinase, NTRK Gene Fusion