NCT04655404

A Pilot Study of Larotrectinib for Newly-Diagnosed High-Grade Glioma With NTRK Fusion

A Pilot and Surgical Study of Larotrectinib for Treatment of Children With Newly-Diagnosed High-Grade Glioma With NTRK Fusion

• Status: Recruiting
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 15 (estimated)
• Sponsor: Nationwide Children's Hospital · Academic / Other
• Sex: All
• Age: 21 Years
• Healthy volunteers: Not accepted

Summary

This is a pilot study that will evaluate disease status in children that have been newly diagnosed high-grade glioma with TRK fusion. The evaluation will occur after 2 cycles of the medication (Larotrectinib) have been given. The study will also evaluate the safety of larotrectinib when given with chemotherapy in your children; as well as the safety larotrectinib when given post-focal radiation therapy.

Detailed description

In this pilot study, we will assess the disease control rate (Continued Complete Response-CCR, Complete Response-CR, Partial Response-PR and Stable Disease-SD) as well as survival rate (overall survival- OS and progression free survival- PFS) in children with newly diagnosed HGG with TRK fusion who receive 2 cycles of larotrectinib monotherapy administered orally, twice daily, at 100 mg/m2 continuously on a 28-day cycle schedule. After 2 monotherapy cycles of larotrectinib, patients with CCR or CR will continue to receive larotrectinib maintenance therapy as monotherapy for a total of 12 cycles. Continuation of treatment beyond 12 cycles, and up to 24 cycles, may be considered for patients on Larotrectinib monotherapy if they are receiving clinical benefit from the study, at the discretion of the treating physician. Patients ≤ 48 months with PR or SD after 2 cycles of larotrectinib will go on to receive combination therapy with standard backbone chemotherapy (BABYPOG or HIT-SKK). Patients \> 48 months of age (or patients ≥ 36 months of age, or patients with DIPG \>18 months of age, at the discretion of the local investigator) will receive focal radiation therapy. A surgical cohort study will be explored whereby patients who have had a tumor biopsy/partial resection at their local institution and are planned to subsequently undergo definitive resection will receive 3-5 days (6-10 doses) of larotrectinib pre-surgery. The study design of this trial requires 15 patients evaluable for disease control and for safety/ toxicity of larotrectinib as monotherapy. The surgical cohort will enroll up to 4 patients and will count towards the total 15 evaluable patients. A minimum of 6 patients will be evaluable for safety toxicity of larotrectinib in combination with standard-of-care chemotherapy or radiotherapy.

Conditions

• High Grade Glioma
• Diffuse Intrinsic Pontine Glioma

Interventions

Type	Name	Description
DRUG	Larotrectinib	1. Larotrectinib monotherapy x2 cycles followed by disease evaluation 2. Larotrectinib with or without chemotherapy backbone
PROCEDURE	Larotrectinib surgical	1. Surgical cohort: Larotrectinib x 3-5 days prior to definitive surgery followed by Larotrectinib monotherapy x2 cycles followed by disease evaluation 2. Larotrectinib with or without chemotherapy backbone

Timeline

• Start date: 2021-04-08
• Primary completion: 2026-12-01
• Completion: 2036-12-01
• First posted: 2020-12-07
• Last updated: 2026-03-18

Locations

21 sites across 5 countries: United States, Australia, Canada, Germany, New Zealand

Regulatory

• FDA-regulated drug study