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

Conditions

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

Eligibility Criteria

Sex

ALL

Age

1 Year - 21 Years

Healthy Volunteers

Accepted

Interventions

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

Study Details

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.

Key Dates

Start date

Aug 3, 2025

Status verified

May 2025

Primary completion

Jul 1, 2029

Completion

Jun 1, 2035

Study Design

Enrollment

15 participants (estimated)

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Lorlatinib Monotherapy
  Lorlatinib administered as monotherapy by PO (per os) or NG (nasogastric) for two 28-day cycles at 115 mg/m2/day (or maximum 200mg/dose), after which disease evaluation by Magnetic Resonance Imaging (MRI) imaging will be performed.
• Experimental: Lorlatinib Combination with BABY POG chemotherapy
  Lorlatinib monotherapy x2 cycles followed by maintenance therapy with lorlatinib (115 mg/m2/day) and BABY-POG chemotherapy backbone (vincristine, cyclophosphamide, cisplatin) The BABYPOG chemotherapy backbone regimen will consist of six 12-week courses. Each course will consist of cycles A, A2 and B, which will be administered consecutively, in 28-day cycles for a total of 72 weeks
• Experimental: Lorlatinib Combination with HIT-SKK chemotherapy
  Lorlatinib monotherapy x2 cycles followed by maintenance therapy with lorlatinib (115 mg/m2/day) and HIT-SKK chemotherapy backbone (cyclophosphamide, vincristine, methotrexate, carboplatin, etposide) The recommended HIT-SKK chemotherapy backbone regimen consists of modular chemotherapy cycles, three courses of 4 blocks each (Element IIS, Element IIIS/1, Element IIIS/2, and Element IVS). Each element will be administered consecutively at 2-3-week intervals. Elements IIS and IVS cycles will be repeated twice thereafter. The entire length of treatment for HIT-SKK will be approximately 42 weeks.
• Experimental: Lorlatinib Maintenance Therapy post RT
  Lorlatinib monotherapy x2 cycles followed by Radiation Therapy and continue lorlatnib maintenance monotherapy (115 mg/m2/day) 28 days post completion of RT for 12 cycles

Primary Outcome Measure

Disease Control Rate [ Time Frame: Day 1 of treatment until the end of cycle 2 (each cycle is 28 days) ]

Central Contacts

• Kelsey H Troyer, PhD
  16147223284
  [email protected]

Locations (10)

Find similar trials in Aurora, CO

Related Studies

• Molecular Analysis of Samples From Patients With Diffuse Intrinsic Pontine Glioma and Brainstem Glioma
  Recruiting · Children's National Research Institute · Washington D.C., District of Columbia
• Safety and Efficacy Study in Recurrent or Progressive Grade III or IV IDH1 Mutated Glioma
  PHASE1/PHASE2 · Recruiting · Neonc Technologies, Inc. · Los Angeles, California
• INdividualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT)
  PHASE2 · Recruiting · Patrick Wen, MD · Birmingham, Alabama
• International Diffuse Intrinsic Pontine Glioma (DIPG)/Diffuse Midline Glioma (DMG) Registry and Repository
  Recruiting · Children's Hospital Medical Center, Cincinnati · Cincinnati, Ohio