A Study to Test the Safety and Efficacy of the Drug Larotrectinib for the Treatment of Tumours With NTRK-fusion in Children

Official Title

A Phase 1/2 Study of the Oral TRK Inhibitor Larotrectinib in Pediatric Patients With Advanced Solid or Primary Central Nervous System Tumours

Summary:

The study is being done to test the safety of a cancer drug called larotrectinib in children. The cancer must have a change in a particular gene (NTRK1, NTRK2 or NTRK3). Larotrectinib blocks the actions of these NTRK genes in cancer cells and can therefore be used to treat cancer.

The first study part (Phase 1) is done to determine what dose level of larotrectinib is safe for children, how the drug is absorbed and changed by their bodies and how well the cancer responds to the drug. The main purpose of the second study part (Phase 2) is to investigate how well and how long different cancer types respond to the treatment with larotrectininb.

Trial Description

Primary Outcome:

• Phase 1: Number of participants in an assigned dose cohort with treatment emergent adverse events (TEAEs) by grade assessed by NCI-CTCAE v 4.03 who experience a DLT
• Phase 1: Number of participants with TEAEs
• Phase 1: Severity of TEAEs
• Phase 2: Overall response rate (ORR) by IRRC

Secondary Outcome:

• Phase 1: Maximum concentration of larotrectinib in plasma (Cmax)
• Phase 1: Area under the concentration versus time curve from time 0 to t (AUC0-t) of larotrectinib in plasma
• Phase 1: Oral clearance (CL/F)
• Phase 1: Cerebral spinal fluid/plasma ratio of larotrectinib
• Phase 1: Maximum tolerated dose (MTD)
• Phase 1: Recommended dose for Phase 2
• Phase 1: Overall Response Rate (ORR)
• Phase 1: Mean change from baseline in Pain scores as assessed by the Wong-Baker Faces scale
• Phase 1: Mean change in Health-related quality of life scores by PedsQL-Core
• Phase 2: Best overall response (BOR)
• Phase 2: Duration of response (DOR)
• Phase 2: Proportion of patients with any tumour regression (i.e., any decrease from baseline of the longest diameters of target lesions) as a best response
• Phase 2: Progression-free survival (PFS)
• Phase 2: Overall survival (OS)
• Phase 2: Number of participants with Treatment emergent adverse events (TEAEs)
• Phase 2: Severity of adverse events as assessed by NCI-CTCAE grading V 4.03
• Phase 2: Clinical Benefit Rate (CBR)
• Phase 2: Concordance coefficient
• Phase 2: Post-operative tumour staging
• Phase 2: Post-operative surgical margin assessment
• Phase 2: Pre-treatment surgical plan to preserve function and cosmetic outcome
• Phase 2: Post-treatment plans to conserve function and cosmetic outcome

The primary objectives are to determine the safety and efficacy of oral larotrectinib in pediatric patients with advanced solid or primary central nervous system (CNS) tumours.

The secondary objectives comprise e.g. the determination of the pharmacokinetic properties, the maximum tolerated dose/ recommended dose and the tumour-type specific efficacy of larotrectinib. In addition, pain status and health-related quality of life of the pediatric patients will be assessed.

View this trial on ClinicalTrials.gov