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 (EPI VITRAKVI)

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)

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.

Study Overview

• Status: Completed
• Conditions: Locally Advanced or Metastatic Infantile Fibrosarcoma Harboring an NTRK Gene Fusion; Infantile Fibrosarcoma
• Intervention / Treatment: Drug: Larotrectinib (Vitrakvi, BAY2757556); Drug: Standard of Care

• Study Type: Observational
• Enrollment (Actual): 93

Contacts and Locations

Study Locations

• France
  • Multiple Locations, France
    • Multiple locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 21 years (Child, Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

The study population comprises of all pediatric patients in the SCOUT study and the eligible historical cohort(s) with a diagnosis of locally advanced or metastatic IFS harboring an NTRK gene fusion.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Medical Treatment Failure	Time to medical treatment failure was defined as the time (months) from the start of treatment to the date of the earliest event from: subsequent systemic treatment, radiation therapy, mutilating surgery or death due to any cause.	up to 5.5 years for participants in SCOUT study and 22.5 years for participants in external historical control

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Subsequent Systemic Treatment	Time to subsequent systemic treatment was defined as the time from start date of Larotrectinib (for SCOUT) or start date of chemotherapy (for historical control cohorts) till the start date of a post-treatment systemic anti-cancer therapy, if any	up to 5.5 years for participants in SCOUT study and 22.5 years for participants in external historical control
Time to Mutilating Surgery Including Limb Amputation	Time to mutilating surgery including limb amputation was defined as the time from start date of Larotrectinib (for SCOUT) or start date of chemotherapy (for historical control cohorts) till the start date of a mutilating surgery (including limb amputation)	up to 5.5 years for participants in SCOUT study and 22.5 years for participants in external historical control
Time to First Radiation Therapy	Time to radiation therapy was defined as the time from start date of Larotrectinib (for SCOUT) or start date of chemotherapy(for historical control cohorts) till the start date of a radiation therapy, if any	up to 5.5 years for participants in SCOUT study and 22.5 years for participants in external historical control
Time to Complete Surgical Resection	Time to complete surgical resection (excluding amputation) was defined as the time from start date of Larotrectinib (for SCOUT) or start date of chemotherapy (for historical control cohorts) till the start date of a complete surgical resection (excluding amputation), if any	up to 5.5 years for participants in SCOUT study and 22.5 years for participants in external historical control
Overall Survival	Number of participants with death due to any cause, alive, or lost to follow-up.	up to 5.5 years for participants in SCOUT study and 22.5 years for participants in external historical control
Number of Participants With Treatment Discontinuation Due to Treatment Emergent Adverse Events	Larotrectinib treatment for the SCOUT study and chemotherapy (first line) for the external historical control cohort(s).	up to 5.5 years for participants in SCOUT study and 22.5 years for participants in external historical control

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

Helpful Links

• VITRAKVI Patient Information
• Click here to find information for studies related to Bayer products. To find this study enter the NCT number or Bayer Study ID in the search field.

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2022
• Primary Completion (Actual): September 13, 2022
• Study Completion (Actual): September 13, 2022

Study Registration Dates

• First Submitted: February 2, 2022
• First Submitted That Met QC Criteria: February 2, 2022
• First Posted (Actual): February 11, 2022

Study Record Updates

• Last Update Posted (Estimated): December 10, 2024
• Last Update Submitted That Met QC Criteria: December 8, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Advanced solid tumors; Larotrectinib; Neurotrophic tyrosine receptor kinase (NTRK); Fusion Positive; Infantile fibrosarcoma (IFS); Tropomyosin Receptor Kinase (TRK) fusion; External control
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms, Connective Tissue; Neoplasms, Fibrous Tissue; Fibrosarcoma
• Other Study ID Numbers: 21767

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No