Brief 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.

Conditions

• High Grade Glioma
• Diffuse Intrinsic Pontine Glioma
• Anaplastic Astrocytoma
• Infant Type Hemispheric Glioma
• Glioblastoma
• Glioblastoma Multiforme
• WHO Grade III Glioma
• WHO Grade IV Glioma
• Diffuse Midline Glioma, H3K27-altered

Intervention / Treatment

• Drug: Lorlatinib
• Drug: Lorlatinib with chemotherapy1
• Drug: Lorlatinib with chemotherapy 2
• Drug: Lorlatinib post Radiation

Primary Outcome Measures

• Disease Control Rate (Day 1 of treatment until the end of cycle 2 (each cycle is 28 days))
  To assess the disease control rate (Complete Response \[CR\], Continued Complete Response \[CCR\], Partial Response \[PR\] and Stable Disease \[SD\]) of lorlatinib in young children with newly diagnosed high-grade glioma with ALK or ROS1 fusion after 2 cycles of lorlatinib monotherapy.
• Number of participants with lorlatinib-related adverse events as assessed by CTCAE v5.0 (From Day 1 of protocol treatment through 30 days following end of protocol treatment)
  Assess and further characterize the safety and toxicity of lorlatinib in pediatric patients newly diagnosed with HGG with a fusion in ALK or ROS. This will be achieved by calculating the number of participants with, as well as frequency and severity of, lorlatinib-related Adverse Events as assessed by CTCAE v5.0

Countries

Australia, Canada, Germany, Netherlands, New Zealand, United States

Locations and Investigators

• Children's Hospital Colorado, Aurora, United States (Not yet recruiting)
  • Holly Lindsay, MD
• Children's National Medical Center, Washington D.C., United States (Not yet recruiting)
  • Eugene Hwang
• Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, United States (Not yet recruiting)
  • Ashley Plant, MD
• Dana-Farber Cancer Institute, Boston, United States (Not yet recruiting)
  • Susan Chi
• Duke University Health System, Durham, United States (Not yet recruiting)
  • David Ashley, MD
• Cincinnati Children's Hospital Medical Center, Cincinnati, United States (Recruiting)
  • Peter de Blank, MD
• Nationwide Children's Hospital, Columbus, United States (Recruiting)
  • Maryam Fouladi, MD, MSc
• Children's Hospital of Philadelphia, Philadelphia, United States (Not yet recruiting)
  • Michael J Fisher, MD
• Texas Children's Hospital, Houston, United States (Not yet recruiting)
  • Patricia Baxter, MD
• Seattle Children's Hospital, Seattle, United States (Not yet recruiting)
  • Erin Crotty, MD
• Sydney Children's Hospital, Randwick, Australia (Not yet recruiting)
  • David Ziegler, MD
• Queensland Children's Hospital, South Brisbane, Australia (Not yet recruiting)
  • Tim Hassall, MD
• Perth Children's Hospital, Perth, Australia (Not yet recruiting)
  • Nicholas G Gottardo, MBChB
• The Hospital for Sick Children (SickKids), Toronto, Canada (Not yet recruiting)
  • Eric Bouffet
• Montreal Children's Hospital, Montreal, Canada (Not yet recruiting)
  • Genevieve Legault, MD
• Hopp Children's Cancer Center at NCT Heidelberg (KiTZ), Heidelberg, Germany (Not yet recruiting)
  • Olaf Witt, MD
• Princess Máxima Center, Utrecht, Netherlands (Not yet recruiting)
  • Jasper van der Lugt
• Starship Children's Hospital, Auckland, New Zealand (Not yet recruiting)
  • Sarah Hunter, MB ChB

Study Officials

• Hamza Gorsi, MD (Study Chair) — Children's Hospital of Michigan
• Susan Chi, MD (Study Chair) — Dana-Farber Cancer Institute
• Maryam Fouladi, MD (Principal Investigator) — Nationwide Children's Hospital