PrOspective Non-interventional study in patients with locally advanced or metastatic TRK fusion cancer treated with larotrectinib (ON-TRK)

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Drug utilisation

  Effectiveness study (incl. comparative)

  Safety study (incl. comparative)
• Data collection methods:
  Primary data collection

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Medicinal product name:
  VITRAKVI
• Study drug International non-proprietary name (INN) or common name:
  LAROTRECTINIB
• Medical condition to be studied:
  NTRK gene fusion overexpression

Population studied

• Short description of the study population:
  Patients with locally advanced or metastatic TRK fusion cancer treated with larotrectinib.
• Age groups:
  • Preterm newborn infants (0 – 27 days)
  • Term newborn infants (0 – 27 days)
  • Infants and toddlers (28 days – 23 months)
  • Children (2 to < 12 years)
  • Adolescents (12 to < 18 years)
  • Adults (18 to < 46 years)
  • Adults (46 to < 65 years)
  • Adults (65 to < 75 years)
  • Adults (75 to < 85 years)
  • Adults (85 years and over)
• Estimated number of subjects:
  300

Study design details

• Study design:
  International, prospective, open-label, multicenter, multi-cohort, non-interventional study.
• Main study objective:
  The primary objective of this study is to describe the safety of larotrectinib in adult and pediatric patients with locally advanced or metastatic TRK fusion cancer, including incidences of all treatment-emergent adverse events (TEAEs) in real-world practice conditions
• Comparators:
  Comparison of outcomes after treatment with larotrectinib versus treatment with an internal comparator cannot be performed in this study, and as such it is not possible to distinguish the effects of treatment versus the natural course of disease or effects from other unknown factors.
• Outcomes:
  1. Number of participants with treatmentemergent adverse events (TEAEs), 2. Severity of TEAEs, 3. Seriousness of TEAEs, 4. Outcome of TEAEs, 5. Causality of TEAEs, 6. Action taken related to larotrectinib treatment. 1. ORR, 2. PFS, 3. OS, 4. (Pediatric cohort) Change in height and weight from baseline by visit, developmental milestones abnormalities and tanner stage abnormalities, 5. Neurological abnormalities, 6. Total dose, starting and ending dose, dose modification during treatment and duration of treatment, 7. DCR, 8. DOR, 9. TTR, 10. ORR,DCR,DOR,TTR,PFS,OS by patient subgroup(s).
• Data analysis plan:
  Statistical analyses will be of explorative and descriptive nature. The study is not designed to support any formal statistical testing. Unless otherwise stated, all CIs will be given at a 2-sided 95% level. All variables will be analyzed descriptively with appropriate statistical methods: categorical variables by frequency tables and continuous variables by sample statistics. Patients who took at least one dose of larotrectinib will be included in the safety analysis set. Patients who took at least one dose of larotrectinib, did not violate a major inclusion/exclusion criterion, and had at least one post baseline assessment after receiving larotrectinib will be included in the full analysis set. Safety data will be analyzed on the safety analysis set, effectiveness data on the full analysis set. Demographic and baseline data will be described for both full and safety analysis sets.