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Lorlatinib for Newly-Diagnosed High-Grade Glioma With ROS or ALK Fusion
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.
Study details:
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) 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. 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. 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 will start at the recommended phase 2 dose of 115 mg/m2/day, 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.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
Exclusion criteria
Eligibility
Age eligible for study : 1 and older
Healthy volunteers accepted : Yes
Gender eligible for study: All
Things to know
Study dates
Study start: 2024-09-01
Primary completion: 2027-09-01
Study completion finish: 2034-09-01
Study type
TREATMENT
Phase
EARLY_PHASE1
Trial ID
NCT06333899
Intervention or treatment
DRUG: Lorlatinib
DRUG: Lorlatinib with chemotherapy1
DRUG: Lorlatinib with chemotherapy 2
DRUG: Lorlatinib post Radiation
Conditions
- • High Grade Glioma
- • Diffuse Intrinsic Pontine Glioma
- • Glioblastoma
- • Glioblastoma Multiforme
- • WHO Grade III Glioma
- • WHO Grade IV Glioma
- • Anaplastic Astrocytoma
- • Infant Type Hemispheric Glioma
- • Diffuse Midline Glioma, H3K27-altered
Find a site
Closest Location:
Sydney Children's Hospital
Research sites nearby
Select from list below to view details:
Sydney Children's Hospital
Randwick, New South Wales, Australia
Queensland Children's Hospital
South Brisbane, Queensland, Australia
Perth Children's Hospital
Perth, Western Australia, Australia
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Participant Group/Arm | Intervention/Treatment |
---|---|
EXPERIMENTAL: Lorlatinib Monotherapy
| DRUG: Lorlatinib
|
EXPERIMENTAL: Lorlatinib Combination with BABY POG chemotherapy
| DRUG: Lorlatinib
|
EXPERIMENTAL: Lorlatinib Combination with HIT-SKK chemotherapy
| DRUG: Lorlatinib
|
EXPERIMENTAL: Lorlatinib Maintenance Therapy post RT
| DRUG: Lorlatinib
|
What is the study measuring?
Primary outcome
Primary Outcome Measure | Primary Outcome Description | Primary Outcome Time Frame |
---|---|---|
Disease Control Rate | 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. | from date on treatment until the end of cycle 2 (each cycle is 28 days) |
Number of participants with lorlatinib-related adverse events as assessed by CTCAE v5.0 | 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 | From Day 1 of protocol treatment through 30 days following end of protocol treatment |
Secondary outcome
Secondary Outcome Measure | Secondary Outcome Description | Secondary Outcome Time Frame |
---|---|---|
Objective Response Rate (ORR) in HGG | To assess the objective response rate (ORR) (Complete Response \[CR\] and Partial Response \[PR\]) of lorlatinib in children with newly diagnosed high-grade glioma with ALK or ROS1 fusion after 2 cycles of lorlatinib monotherapy. | From Day 1 of protocol treatment through 30 days following end of protocol treatment |
Overall Survival (OS) in HGG | To assess overall (OS) of children with high-grade gliomas treated with a lorlatinib-containing regimen at 1, 3 and 5 years and compare it to historical data from BABYPOG and HIT-SKK. | From date on treatment until date of death due to any cause or date of last follow-up, assessed up to 60 months |
Progression-Free Survival in HGG | To assess progression-free survival (PFS) of children with high-grade gliomas treated with a lorlatinib-containing regimen at 1, 3 and 5 years and compare it to historical data from BABYPOG and HIT-SKK. | From date on treatment until date of Progressive Disease or death due to any cause or date of last follow-up, assessed up to 5 years |
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