Larotrectinib versus historical standard of care in patients with infantile fibrosarcoma: protocol of EPI-VITRAKVI

Abstract

The EPI VITRAKVI study is a retrospective study designed to place the results of the single-arm Phase I/II larotrectinib SCOUT trial into context by comparison with external historical controls. Its primary objective is to compare the time to medical treatment failure between larotrectinib and the historical standard of care (chemotherapy) in patients with infantile fibrosarcoma. External historical cohorts have been selected by using objective criteria. The Inverse Probability of Treatment Weighting method will be used to adjust for potential confounding. The current publication illustrates how an external control arm study can complement data from a single-arm trial and addresses uncertainties encountered in the assessment of therapies targeting rare abnormalities where randomized controlled trials are considered not feasible.

Clinical Trial Registration: NCT05236257 (ClinicalTrials.gov)

Plain language summary

Larotrectinib compared with chemotherapy in patients with infantile fibrosarcoma: protocol of EPI-VITRAKVI: Infantile fibrosarcoma (IFS) is a rare type of childhood cancer that commonly affects the legs and arms. In IFS cancers, the units which carry the information that determines your traits (genes), typically have specific changes which leads to the creation of an altered fusion protein, a protein which is created by joining parts of two different genes. This altered fusion protein can cause cancer cells to survive and to grow. Larotrectinib works by blocking the altered fusion protein and is already available in Europe and in many other countries. It is approved for prescription to patients with the altered fusion protein, whose cancer has spread to nearby tissues and/or lymph nodes or to other parts of the body. Since IFSs a rare disease, previous studies did not compare larotrectinib with the standard of care, which is chemotherapy. The main purpose of our study is to collect more results on how well larotrectinib works compared with chemotherapy taken from real world evidence data. The present publication explains how such a comparison can be made and how such a study can help in the assessment of treatments that target rare diseases.

Keywords::

• external historical control
• infantile fibrosarcoma
• larotrectinib
• NTRK
• tropomyosin receptor kinase inhibitor

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/fon-2023-0114

Acknowledgments

The authors wish to thank the Institut Curie and the Cooperative Weichteilsarkom Studiengruppe for providing data from the external historical control cohorts.

Ethical disclosure

This study was approved by the French Ethics and Scientific Committee for Health Research, Studies and Evaluations (Comité Ethique et Scientifique pour les Recherches, les Etudes et les Evaluations dans le domaine de la Santé, CESREES) and received an exemption from individual patient information from the French Data Protection Authority (Comité National de l’Informatique et des Libertés, CNIL). It has been registered at Clinicaltrials.gov (NCT05236257). A study report will be written and transmitted to the applicable competent authorities. Study results will be reviewed and interpreted by external experts and are intended to be disseminated in peer-reviewed journals and medical conferences under the oversight of the Market Authorization Holder.

Financial & competing interests disclosure

This research is supported by Bayer HealthCare SAS. J-B Colin, M Kurtinecz, M Feuilly, P Arvis and SK Khadir are Bayer employees. In addition, D Orbach had a consultant activity for Bayer and Roche and is an Independent Data Monitoring Committee (IDMC) member for a Lilly product and is a consultant for Novartis Pharma France and Eusapharm. The Tag and Trak project was supported by a grant from Enfant-Cancers et Sante. D Orbach and M Carton do consultant work for the French Larotrectinib Transparency Committee (consultancy agreement signed with the institution). An independent translational research project conducted by them is partially supported by Bayer (Investigation Supported research). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Medical writing and editorial support were provided by Dorien O (Keyrus Life Science) and were funded by Bayer.

Additional information

Funding

This research is supported by Bayer HealthCare SAS. J-B Colin, M Kurtinecz, M Feuilly, P Arvis and SK Khadir are Bayer employees. In addition, D Orbach had a consultant activity for Bayer and Roche and is an Independent Data Monitoring Committee (IDMC) member for a Lilly product and is a consultant for Novartis Pharma France and Eusapharm. The Tag and Trak project was supported by a grant from Enfant-Cancers et Sante. D Orbach and M Carton do consultant work for the French Larotrectinib Transparency Committee (consultancy agreement signed with the institution). An independent translational research project conducted by them is partially supported by Bayer (Investigation Supported research). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.