A Study Called EPI VITRAKVI to Compare Treatment Results in Patients With Infantile Fibrosarcoma (IFS), a Type of Connective Soft Tissue Cancer, Who Received a Treatment Called Larotrectinib From a Study Called SCOUT With Patient Data From an External Database

Study Overview
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Brief Summary
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This is an observational study in which data from the past of children and young people with a specific cancer, called NTRK gene fusion positive infantile fibrosarcoma (IFS) is studied. IFS is a rare type of childhood cancer that commonly affects legs and arms. IFS cancers typically have specific changes in their building plans (genes) called NTRK gene fusion. NTRK stands for the specific gene that has been altered, the neurotrophic tyrosine kinase (NTRK) gene. This change to the building plan leads to the creation of an altered protein known as a TRK fusion protein, which can cause cancer cells to grow and to survive. The specific cancer is therefore also called TRK (tropomyosin receptor kinase) fusion-positive IFS. The study drug, larotrectinib (also called BAY2757556) works by blocking the altered TRK fusion protein. Larotrectinib is already available in Europe and in many other countries and is approved for doctors to prescribe to patients with NTRK gene fusion cancer which has spread to nearby tissues and/or lymph nodes or to other parts of the body. In France, HAS (the French authority in charge of evaluating health products and technologies) gave a positive opinion for the reimbursement of larotrectinib but only in the pediatric patients with IFS or another STS harboring a NTRK gene fusion, which is locally advanced or metastatic, and refractory or in relapse mainly due to the lack of comparative evidence. The main purpose of this study is to collect more data to learn how well larotrectinib works compared with current standard of care chemotherapy in people up to 21 years of age with NTRK gene fusion positive IFS that has spread to nearby tissues and/or lymph nodes (locally advanced) or other parts of the body (metastatic). To see how well larotrectinib works, researchers will make a comparison between how long larotrectinib works well and how long the standard of care works well. Working well means that the treatments can prevent the following from happening: need for a new treatment for the cancer need for radiation therapy for the cancer need for surgery to treat the cancer, but which causes major damage to body parts death. In addition to the above, data about medical problems related to the treatments in both groups and that may have required to stop the treatment will be compared. The data for the comparison will come from an ongoing international study called SCOUT which was started in December 2015 (larotrectinib group) international databases (standard of care chemotherapy group). Data will be from the year 2000 up to the present. There will be no required visits with a study doctor or required tests in this study.

Official Title
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A Comparison of Clinical Outcomes in Infantile Fibrosarcoma (IFS) Patients Treated With Larotrectinib in the Phase I/II SCOUT Study Versus (an) External Historical Cohort(s)

Conditions
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Locally Advanced or Metastatic Infantile Fibrosarcoma Harboring an NTRK Gene Fusion, Infantile Fibrosarcoma

Intervention / Treatment
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* Drug: Larotrectinib (Vitrakvi, BAY2757556)
* Drug: Standard of Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≤ 21 years old. Locally advanced or metastatic Infantile Fibrosarcoma (IFS). Identification of an NTRK gene fusion by a molecular biology assay. Patients with available information on clinical, radiological characteristics of their tumor, therapies administered and outcomes. Patients receiving larotrectinib in the SCOUT trial. Patients receiving at least chemotherapy drugs in the historical control cohort(s). No opposition from the patients and/or representatives for data use. Exclusion Criteria: Patients treated with TRK inhibitors in the historical control cohort(s). Patients with documented absence of NTRK gene fusion. Patients participating in an investigational program with interventions outside of routine clinical practice.

Ages Eligible for Study
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Maximum Age: 21 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Larotrectinib<br>Pediatric patients with IFS harboring an NTRK gene fusion who have been enrolled in the SCOUT study. | Drug: Larotrectinib (Vitrakvi, BAY2757556)<br>* Pediatric patients with IFS harboring an NTRK gene fusion.<br>|
| Standard care<br>Pediatric patients with IFS harboring an NTRK gene fusion in the eligible external cohort(s). | Drug: Standard of Care<br>* Standard of care for the patients from the eligible external cohorts.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to treatment failure | Defined as the time (months) from the start of treatment to the date of the following events, whichever comes first: subsequent systemic treatment, radiation therapy, mutilating surgery or death due to any cause. | Retrospective data analysis 2000 to July 2021 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to subsequent systemic treatment | Calculated from the start date of larotrectinib treatment for the SCOUT study and start date of chemotherapy (first line) for the external historical control cohort(s) to the start date of a post-treatment systemic anti-cancer therapy, if any. | Retrospective data analysis 2000 to July 2021 | 
| Time to mutilating surgery including limb amputation | Calculated from the start date of larotrectinib treatment for the SCOUT study and start date of chemotherapy (first line) for the external historical control cohort(s) to the date of a post-treatment mutilating surgery including limb amputation, if any. | Retrospective data analysis 2000 to July 2021 | 
| Time to radiation therapy. | Calculated from the start date of larotrectinib treatment for the SCOUT study and start date of chemotherapy (first line) for the external historical control cohort(s) to the start date of a post-treatment radiation therapy, if any. | Retrospective data analysis 2000 to July 2021 | 
| Time to complete surgical resection | Calculated from the start date of larotrectinib treatment for the SCOUT study and start date of chemotherapy (first line) for the external historical control cohort(s) to the date of a post-treatment complete surgical resection (excluding amputation), if any. | Retrospective data analysis 2000 to July 2021 | 
| Overall Survival (OS) | Start date of larotrectinib treatment for the SCOUT study and start date of chemotherapy (first line) for the external historical control cohort(s), Date of death due to any cause, if applicable, or, Last date of patient follow-up for patients alive and lost to follow-up, if applicable. | Retrospective data analysis 2000 to July 2021 | 
| Number of participants with treatment discontinuation due to treatment-related adverse events | Larotrectinib treatment for the SCOUT study and chemotherapy (first line) for the external historical control cohort(s). | Retrospective data analysis 2000 to July 2021 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced solid tumors, Infantile fibrosarcoma (IFS), Neurotrophic tyrosine receptor kinase (NTRK), Fusion Positive, Tropomyosin Receptor Kinase (TRK) fusion, Larotrectinib, External control