Trials / Recruiting

RecruitingNCT06333899

Lorlatinib for Newly-Diagnosed High-Grade Glioma With ROS or ALK Fusion

A Pilot Study of Lorlatinib for Treatment of Children With Newly Diagnosed High-Grade Glioma With ROS-1 (ROS Proto-Oncogene 1, Receptor Tyrosine Kinase) or ALK (Anaplastic Lymphoma Kinase) Fusion

Status: Recruiting
Phase: EARLY_Phase 1
Study type: Interventional
Enrollment: 15 (estimated)

Sponsor: Nationwide Children's Hospital · Academic / Other
Sex: All
Age: 1 Year – 21 Years
Healthy volunteers: Accepted

Summary

The goal of this study is to determine the response of the study drug loratinib in treating children who are newly diagnosed high-grade glioma with a fusion in ALK or ROS1. It will also evaluate the safety of lorlatinib when given with chemotherapy or after radiation therapy.

Detailed description

This is a multi-institutional clinical trial of lorlatinib in children newly diagnosed with High Grade Glioma (HGG) harboring ROS1 (ROS Proto-Oncogene 1, Receptor Tyrosine Kinase) or ALK (anaplastic lymphoma kinase) fusions. In this pilot study, investigators will assess the disease control rate (Continued Complete Response (CCR), Complete Response (CR), Partial Response (PR), and Stable Disease (SD)) of lorlatinib, and feasibility and safety of lorlatinib administration in combination with standard chemotherapy in children with newly diagnosed HGG with ROS or ALK fusions who receive 2 cycles of lorlatinib administered orally, once daily, at 115 mg/m2/day (or maximum of 200mg/dose) for pediatric patients, and 150mg/dose for patients \>18 years, continuously. Secondary objectives include overall survival (OS) and progression free survival (PFS) lorlatinib as a single agent and in combination with standard chemotherapy used in children ≤ 48 months with HGG, or post focal radiotherapy in children \> 48 months of age. Children with HGG who have a CCR or CR after 2 cycles of therapy will continue to receive single agent lorlatinib for a total of 12xs 28-day cycles. Continuation of treatment beyond 12 cycles, and up to maximum 26 cycles, may be considered for patients on lorlatinib monotherapy if they are receiving clinical benefit from the study, at the discretion of the treating physician after discussion with Study Chairs. Patients with PR or SD after 2 cycles of lorlatinib monotherapy will go on to receive lorlatinib either in combination with standard backbone chemotherapy (BABYPOG or HIT-SKK, investigator's choice) or post standard radiotherapy, based on the patient's age. Patients with PD after 2 cycles will be taken off protocol therapy. This study will be a part of the TarGeT, molecularly-guided umbrealla trial in children, adolescents, and young adults newly diagnosed with HGG, including diffuse intrinsic pontine glioma (DIPG)/diffuse midline glioma (DMG). Patients will undergo (1) upfront comprehensive tumor molecular profiling using multi-omic approach with rapid return of results, (2) stratification to biologically-targeted treatment arms to assess treatment efficacy, and (3) longitudinal evaluation of peripheral blood, cerebrospinal fluid (CSF), and/or tumor tissue as well as neuro-imaging to identify biomarkers predictive of response, recurrence, and resistance. Based on recent trials conducted in this patient population, investigators conservatively estimate that 1 child with newly diagnosed DIPG or HGG with either ROS1 or ALK fusion will be enrolled every 2 months on this study. Patients ≤18 years will start at the recommended phase 2 dose of 115 mg/m2/day and patients \>18 years will start at 150mg/dose. All patients will be treated continuously for 28 days, and one dose de-de-escalations will be allowed. A maximum of 15 eligible patients will be enrolled, anticipated over 2.5 years.

Conditions

Interventions

Type	Name	Description
DRUG	Lorlatinib	Continue maintenance monotherapy for total 12 cycles
DRUG	Lorlatinib with chemotherapy1	Continue lorlatinib with BABY-POG chemotherapy backbone for 72 weeks
DRUG	Lorlatinib with chemotherapy 2	Continue lorlatinib with HIT-SKK chemotherapy backbone for 42 weeks
DRUG	Lorlatinib post Radiation	Continue lorlatinib monotherapy 28 days post completion of radiation therapy for 12 cycles

Timeline

Start date: 2025-08-03
Primary completion: 2029-07-01
Completion: 2035-06-01
First posted: 2024-03-27
Last updated: 2026-03-12

Locations

18 sites across 6 countries: United States, Australia, Canada, Germany, Netherlands, New Zealand

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT06333899. Inclusion in this directory is not an endorsement.