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
Nationwide Children's Hospital
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.
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…
Eligibility
- Age range
- 1–21 years
- Sex
- All
- Healthy volunteers
- Yes
Inclusion Criteria: 1. Patients must be ≥ 12 months and ≤ 21 years of age at the time of study enrollment on TarGeT-SCR. 2. Diagnosis: Patients with newly diagnosed high-grade glioma (HGG), including diffuse intrinsic pontine gliomas (DIPG), whose tumors harbor an ALK or ROS-1 fusion alteration are eligible. Patients must have had histologically verified high-grade glioma from diagnostic biopsy or resection. For the diagnosis of DIPG, patients must have a tumor with pontine epicenter and diffuse involvement of at least 2/3 of the pons, with histopathology consistent with diffuse WHO Grade…
Interventions
- DrugLorlatinib
Continue maintenance monotherapy for total 12 cycles
- DrugLorlatinib with chemotherapy1
Continue lorlatinib with BABY-POG chemotherapy backbone for 72 weeks
- DrugLorlatinib with chemotherapy 2
Continue lorlatinib with HIT-SKK chemotherapy backbone for 42 weeks
- DrugLorlatinib post Radiation
Continue lorlatinib monotherapy 28 days post completion of radiation therapy for 12 cycles
Locations (18)
- Children's Hospital ColoradoAurora, Colorado
- Children's National Medical CenterWashington D.C., District of Columbia
- Ann & Robert H. Lurie Children's Hospital of ChicagoChicago, Illinois
- Dana-Farber Cancer InstituteBoston, Massachusetts
- Duke University Health SystemDurham, North Carolina
- Cincinnati Children's Hospital Medical CenterCincinnati, Ohio