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 LOXO-101 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 with adverse events
  • Phase 1: Severity of adverse events
  • 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 of larotrectinib in plasma (AUC)
  • 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: Pain level
  • Phase 1: Health-related quality of life by PedsQL-Core
  • Phase 2: Overall Response Rate (ORR) by investigator
  • Phase 2: Duration of response (DOR) by IRRC
  • Phase 2: Duration of response (DOR) by investigator
  • Phase 2: Proportion of subjects with any tumour regression as a best response
  • Phase 2: Progression-free survival (PFS) after larotrectinib
  • Phase 2: Overall survival time
  • Phase 2: Number of participants with adverse events
  • Phase 2: Severity of adverse events
  • Phase 2: Clinical benefit rate (CBR) by IRRC
  • Phase 2: Clinical benefit rate (CBR) by investigator
  • Phase 2: Concordance coefficient
  • Phase 2: Post-operative stage in patients treated with larotrectinib
  • Phase 2: Surgical margin status in patients treated with larotrectinib
  • Phase 2: Descriptive analysis of pretreatment surgical plan
  • Phase 2: Descriptive analysis of post-treatment plans
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

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Resources

Canadian Cancer Society

These resources are provided in partnership with the Canadian Cancer Society