Study to Learn More About the Safety and Effectiveness of the Drug VITRAKVI During Routine Use in Patients With TRK Fusion Cancer Which is Locally Advanced or Spread From the Place Where it Started to Other Places in the Body

Study Overview
=================
Brief Summary
-----------------
In this observational study researcher want to learn more about the effectiveness of drug VITRAKVI (generic name: larotrectinib) and how well the drug is tolerated during routine use in patients with TRK fusion cancer which is locally advanced or spread from the place where it started to other places in the body. TRK fusion cancer is a term used to describe a variety of common and rare cancers that are caused by a change to the NTRK (Neurotrophic Tyrosine Kinase) gene called a fusion. During this fusion, an NTRK gene joins together, or fuses, with a different gene. This joining results in the activation of certain proteins (TRK fusion proteins), which can cause cancer cells to multiply and form a tumor. VITRAKVI is an approved drug that blocks the action of the NTRK gene fusion. This study will enroll adult and paediatric patients suffering from a solid tumor with NTRK gene fusion for whom the decision to treat their disease with VITRAKVI has been made by their treating physicians. During the study, patients' medical information such as treatment information with VITRAKVI, other medication or treatments, changes in disease status and other health signs and symptoms will be collected within the normal medical care by the treating doctor. Participants will be observed over a period from 24 to 60 months.

Official Title
-----------------
PrOspective Non-interventional Study in Patients With Locally Advanced or Metastatic TRK Fusion Cancer Treated With Larotrectinib

Conditions
-----------------
Locally Advanced or Metastatic Solid Tumor Harboring an NTRK Gene Fusion

Intervention / Treatment
-----------------
* Drug: larotrectinib(Vitrakvi, BAY2757556)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult and pediatric (from 1 month to 18-year-old) patients Patients with locally advanced or metastatic solid tumor harboring an NTRK gene fusion. NTRK (NTRK1, NTRK2, and NTRK3) gene fusions will be identified locally. Acceptable methods of detection of NTRK gene fusion include NGS, fluorescence in situ hybridization (FISH), reverse-transcription polymerase chain reaction (rt-PCR) or any other genomic testing able to detect NTRK gene fusion. If a pan-TRK IHC method is used, this result needs to be accompanied with the results using one of the other methods noted above. Life expectancy of at least 3 months based on clinical judgement Decision to treat with larotrectinib made by the treating physician prior to study enrollment Patients can also be enrolled if the initial visit (larotrectinib start date) occurred within 2 months ±3 days prior to informed consent signed date Signed informed consent form For patients under legal age, signed assent by the patient (where applicable) and parental/legal guardian signed informed consent is required Exclusion Criteria: Any contraindications as listed in the local approved product information Pregnancy Participation in an investigational program with interventions outside of routine clinical practice Prior treatment with larotrectinib or other kinase inhibitor with TRK inhibition Patients with NTRK gene amplification or NTRK point mutation

Ages Eligible for Study
-----------------
Minimum Age: 1 Month

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| GI<br>adult patients with gastrointestinal (GI) cancer | Drug: larotrectinib(Vitrakvi, BAY2757556)<br>* In the study, patients treated under local standard of care clinical practice; all decisions in terms of diagnostic procedures, treatments, management of the disease, and resource utilization are fully dependent on mutual agreement between the patient and the attending physician, without interference by the study initiator or study protocol<br>|
| H&N<br>adult patients with head and neck (H&N) cancer | Drug: larotrectinib(Vitrakvi, BAY2757556)<br>* In the study, patients treated under local standard of care clinical practice; all decisions in terms of diagnostic procedures, treatments, management of the disease, and resource utilization are fully dependent on mutual agreement between the patient and the attending physician, without interference by the study initiator or study protocol<br>|
| STS<br>adult patients with soft tissue sarcoma (STS) | Drug: larotrectinib(Vitrakvi, BAY2757556)<br>* In the study, patients treated under local standard of care clinical practice; all decisions in terms of diagnostic procedures, treatments, management of the disease, and resource utilization are fully dependent on mutual agreement between the patient and the attending physician, without interference by the study initiator or study protocol<br>|
| CNS<br>adult patients with primary central nervous system (CNS) cancer | Drug: larotrectinib(Vitrakvi, BAY2757556)<br>* In the study, patients treated under local standard of care clinical practice; all decisions in terms of diagnostic procedures, treatments, management of the disease, and resource utilization are fully dependent on mutual agreement between the patient and the attending physician, without interference by the study initiator or study protocol<br>|
| Lung<br>adult patients with lung cancer | Drug: larotrectinib(Vitrakvi, BAY2757556)<br>* In the study, patients treated under local standard of care clinical practice; all decisions in terms of diagnostic procedures, treatments, management of the disease, and resource utilization are fully dependent on mutual agreement between the patient and the attending physician, without interference by the study initiator or study protocol<br>|
| Melanoma<br>adult patients with melanoma | Drug: larotrectinib(Vitrakvi, BAY2757556)<br>* In the study, patients treated under local standard of care clinical practice; all decisions in terms of diagnostic procedures, treatments, management of the disease, and resource utilization are fully dependent on mutual agreement between the patient and the attending physician, without interference by the study initiator or study protocol<br>|
| Pediatric<br>all pediatric patients regardless of tumor type will be enrolled under this cohort | Drug: larotrectinib(Vitrakvi, BAY2757556)<br>* In the study, patients treated under local standard of care clinical practice; all decisions in terms of diagnostic procedures, treatments, management of the disease, and resource utilization are fully dependent on mutual agreement between the patient and the attending physician, without interference by the study initiator or study protocol<br>|
| other<br>patients with other tumor types | Drug: larotrectinib(Vitrakvi, BAY2757556)<br>* In the study, patients treated under local standard of care clinical practice; all decisions in terms of diagnostic procedures, treatments, management of the disease, and resource utilization are fully dependent on mutual agreement between the patient and the attending physician, without interference by the study initiator or study protocol<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-emergent adverse events (TEAEs) |  | Up to 30 days after last dose | 
| Severity of TEAEs |  | Up to 30 days after last dose | 
| Seriousness of TEAEs |  | Up to 30 days after last dose | 
| Outcome of TEAEs |  | Up to 30 days after last dose | 
| Causality of TEAEs |  | Up to 30 days after last dose | 
| Action taken related to larotrectinib treatment |  | Up to 30 days after last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) |  | Up to 8 years | 
| Disease control rate (DCR) |  | Up to 8 years | 
| Duration of response (DOR) |  | Up to 8 years | 
| Time to response (TTR) |  | Up to 8 years | 
| Progression-free survival (PFS) |  | Up to 8 years | 
| Overall survival (OS) |  | Up to 8 years | 
| Total dose |  | Up to 8 years | 
| Starting and ending dose |  | Up to 8 years | 
| Dose modification during treatment |  | Up to 8 years | 
| Duration of treatment (DOT) |  | Up to 8 years | 
| ORR by patient subgroup(s) |  | Up to 8 years | 
| DCR by patient subgroup(s) |  | Up to 8 years | 
| DOR by patient subgroup(s) |  | Up to 8 years | 
| TTR by patient subgroup(s) |  | Up to 8 years | 
| PFS by patient subgroup(s) |  | Up to 8 years | 
| OS by patient subgroup(s) |  | Up to 8 years | 
| Number of patients with change in height and weight from baseline by visit, neurological abnormalities (normal/abnormal) | for all patients | Up to 8 years | 
| Number of patients with abnormal developmental milestones | Pediatric cohort only | Up to 8 years | 
| Number of patients with abnormal Tanner stage | Pediatric cohort only | Up to 8 years |