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

ConditionsHigh Grade GliomaDiffuse Intrinsic Pontine GliomaAnaplastic AstrocytomaInfant Type Hemispheric GliomaGlioblastomaGlioblastoma MultiformeWHO Grade III GliomaWHO Grade IV GliomaDiffuse Midline Glioma, H3K27-altered
Trial statusRecruiting
Trial phaseEarly Phase 1
Trial typeInterventional
Biological sexAll
Age1-21
SponsorNationwide Children's Hospital

About this trial

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.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

Patients must be ≥ 12 months and ≤ 21 years of age at the time of study enrollment on TarGeT-SCR.

Patients must not have received any prior anti-cancer chemotherapy.

Prior use of corticosteroids is allowed (see below

Disqualifiers

Peripheral absolute neutrophil count (ANC) ≥ 1000/μL

Platelet count ≥ 100,000/μL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)

Total bilirubin ≤ 2 × institutional upper limit of normal

AST(aspartate aminotransferase)/ALT(alanine transaminase) ≤ 2.5 × institutional upper limit of normal 6.4 Adequate Pulmonary Function Defined as: Pulse oximetry > 94% on room air if there is clinical indication for determination (e.g. dyspnea at rest).

Trial design

Design model

Parallel

Treatments tested in this trial

  • 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

Treatment groups

15 Participants
are divided into 4 treatment groups
Group A: Lorlatinib MonotherapyExperimental treatment 1 intervention
Group B: Lorlatinib Combination with BABY POG chemotherapyExperimental treatment 2 interventions
Group C: Lorlatinib Combination with HIT-SKK chemotherapyExperimental treatment 2 interventions
Group D: Lorlatinib Maintenance Therapy post RTExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

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.

Time frame
Day 1 of treatment until the end of cycle 2 (each cycle is 28 days)
2

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

Time frame
From Day 1 of protocol treatment through 30 days following end of protocol treatment

Secondary outcomes

1

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.

Time frame
From Day 1 of protocol treatment through 30 days following end of protocol treatment
2

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.

Time frame
Day 1 of treatment until date of death due to any cause or date of last follow-up, assessed up to 60 months
3

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.

Time frame
Day 1 of treatment until date of Progressive Disease or death due to any cause or date of last follow-up, assessed up to 5 years
4

Associations between genomic tumor alterations with radiographic response

Explore longitudinal associations of genomic, transcriptomic, epigenetic, and/or immunologic alterations of tumor at diagnosis, recurrence, or autopsy with radiographic response and advanced neuro-imaging measures.

Time frame
From diagnosis through the end of follow-up period.

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Nationwide Children's Hospital

Lead sponsor

Pfizer

Collaborator

Source ClinicalTrials.gov
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