High Grade GliomaEarly Phase 1NCT06333899
Lorlatinib for Newly-Diagnosed High-Grade Glioma With ROS or ALK Fusion
A Early Phase 1 study testing Lorlatinib, Lorlatinib with chemotherapy1 and Lorlatinib with chemotherapy 2 in people with High Grade Glioma and Diffuse Intrinsic Pontine Glioma, run by Nationwide Children's Hospital at 18 sites in 6 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 year to 21 yearsHealthy volunteers can take part
- Conditions the study is for
- High Grade Glioma, Diffuse Intrinsic Pontine Glioma, Anaplastic Astrocytoma
- What is being tested?
- Lorlatinib, Lorlatinib with chemotherapy1 and Lorlatinib with chemotherapy 2
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 18 sitesin 6 countries
- Study dates
- 3 Aug 2025to 1 Jun 2035
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 21 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- Patients must be ≥ 12 months and ≤ 21 years of age at the time of study enrollment on TarGeT-SCR.
- 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 2-4. All other HGGs must be Grade 3 or 4.
- Disease Status:
- Patients with disseminated DIPG or HGG are eligible only if the patient is to receive chemotherapy only, i.e. no craniospinal RT is intended to be given. MRI of spine must be performed if disseminated disease is suspected clinically by the treating physicians. Patients with primary spinal tumors are eligible only if the patient is to receive either chemotherapy or focal radiation therapy, i.e., no craniospinal RT is intended to be given. Patients with leptomeningeal disease only, with no definitive identifiable primary tumor, and documented ALK or ROS-1 fusion, must be discussed with the Study Chair on a case-by-case basis.
- Performance Level:
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- Karnofsky ≥ 50% for patients > 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age (See Appendix I). Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
- Prior Therapy:
- Patients must not have received any prior anti-cancer chemotherapy.
- Prior use of corticosteroids is allowed (see below Exclusion Criteria)
- Organ Function Requirements 6.1 Adequate Bone Marrow Function Defined as:
- 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)
- Hemoglobin >8 g/dL (may receive transfusions) 6.2 Adequate Renal Function Defined as:
- Serum creatinine within normal institutional limits OR Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2 6.3 Adequate Liver Function Defined as:
- 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).
- 6.5Adequate Cardiac Function Defined as: QTc ≤ 470 msec (by Bazett formula) 6.6 Adequate Neurologic Function Defined as: Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled.
- 6.7 Informed Consent: All patients and/or their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines
Who cannot join
- Pregnant or breast-feeding women will not be entered on this study due to unknown risks of fetal and teratogenic adverse events as seen in animal/human studies. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
- Females of reproductive potential must use an effective non-hormonal method of contraception, since lorlatinib can render hormonal contraceptives ineffective, during study treatment and for at least 6 months after the final dose. Males with female partners of reproductive potential must use effective contraception during treatment with lorlatinib and for 3 months after the final dose.
- Concomitant Medications
- Investigational Agents/Drugs: Patients who have previously received or are currently receiving another investigational drug are not eligible.
- Anti-cancer Agents: Patients who have previously received or are currently receiving other anti-cancer agents, including chemotherapy, immunotherapy, monoclonal antibodies, biologic or targeted therapy, are not eligible
- Infection: Patients must not have any active, uncontrolled systemic bacterial, viral or fungal infection.
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- Patients who have received prior solid organ transplantation are not eligible.
- Patients must not have malabsorption syndrome or other condition affecting oral absorption.
- Patients must not be receiving any treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor or inducer. Discontinue strong CYP3A inducers for 3 plasma half-lives of the strong CYP3A inducer prior to treatment with loraltinib. Moderate inducers of CYP3A4 should be avoided
- Avoid concomitant use of lorlatinib with certain CYP3A substrates, for which minimal concentration changes may lead to serious therapeutic failures. If concomitant use is unavoidable, increase the CYP3A substrate dosage in accordance with approved product labeling.
- P-glycoprotein (P-gp) substrates: Lorlatinib is considered a moderate P-gp inducer. Co-administration of lorlatinib with P-gp substrates including but not limited to digoxin should be avoided as the concentration of these drugs may be reduced by lorlatinib.
- Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.
- Patients with a known personal history of acute or chronic severe psychiatric disorders or current history of suicidal ideation and history of suicide attempt.
Trial locations and contacts
18 sites in 6 countries. Contact the study team or a site near you to ask about taking part.
18 sites in 6 countries
United States10 sites, 10 recruiting
- Not yet recruiting
Children's Hospital Colorado
Aurora, Colorado, 80045
Holly Lindsay, MD, holly.lindsay@childrenscolorado.org
- Not yet recruiting
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Susan Chi, Susan_chi@dfci.harvard.edu
- Not yet recruiting
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
Ashley Plant, MD, Aplant@luriechildrens.org
- Recruiting
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Peter de Blank, MD, Peter.deBlank@cchmc.org
- Recruiting
Nationwide Children's Hospital
Columbus, Ohio, 43235
Maryam Fouladi, MD, MSc, Maryam.fouladi@nationwidechildrens.org
- Not yet recruiting
Duke University Health System
Durham, North Carolina, 27708
David Ashley, MD, david.ashley@duke.edu
- Not yet recruiting
Texas Children's Hospital
Houston, Texas, 77030
Patricia Baxter, MD, pabaxter@txch.org
- Not yet recruiting
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Michael J Fisher, MD, fisherm@email.chop.edu
- Not yet recruiting
Seattle Children's Hospital
Seattle, Washington, 98105
Erin Crotty, MD, erin.crotty@seattlechildrens.org
- Not yet recruiting
Children's National Medical Center
Washington D.C., District of Columbia, 20010
Eugene Hwang, ehwang@childrensnational.org
Australia3 sites, 3 recruiting
- Not yet recruiting
Perth Children's Hospital
Perth, Western Australia, 6000
Nicholas G Gottardo, MBChB, nick.gottardo@health.wa.gov.au
- Not yet recruiting
Sydney Children's Hospital
Randwick, New South Wales, 2031
David Ziegler, MD, d.ziegler@unsw.edu.au
- Not yet recruiting
Queensland Children's Hospital
South Brisbane, Queensland, 4101
Tim Hassall, MD, tim.hassall@health.qld.gov.au
Canada2 sites, 2 recruiting
- Not yet recruiting
Montreal Children's Hospital
Montreal, Quebec, H4A3J1
Genevieve Legault, MD, Genevieve.legault4@mcgill.ca
- Not yet recruiting
The Hospital for Sick Children (SickKids)
Toronto, Ontario, M5G1X8
Eric Bouffet, eric.bouffet@sickkids.ca
Germany1 site, 1 recruiting
- Not yet recruiting
Hopp Children's Cancer Center at NCT Heidelberg (KiTZ)
Heidelberg, Baden-Wurttemberg, 69120
Olaf Witt, MD, o.witt@kitz-heidelberg.de
Netherlands1 site, 1 recruiting
- Not yet recruiting
Princess Máxima Center
Utrecht, 3720
Jasper van der Lugt, J.vanderLugt@prinsesmaximacentrum.nl
New Zealand1 site, 1 recruiting
- Not yet recruiting
Starship Children's Hospital
Auckland, Grafton, 1023
Sarah Hunter, MB ChB, +64 9 367 0000, SHunter@adhb.govt.nz
About this study
Official title: 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
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.
Read the detailed 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 of lorlatinib administered orally, once daily, at 115 mg/m2/day (or maximum of 200mg/dose) for pediatric patients, and 150mg/dose for patients >18 years, 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 after discussion with Study Chairs. 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.
This study will be a part of the TarGeT, molecularly-guided umbrealla trial in children, adolescents, and young adults newly diagnosed with HGG, including diffuse intrinsic pontine glioma (DIPG)/diffuse midline glioma (DMG). Patients will undergo (1) upfront comprehensive tumor molecular profiling using multi-omic approach with rapid return of results, (2) stratification to biologically-targeted treatment arms to assess treatment efficacy, and (3) longitudinal evaluation of peripheral blood, cerebrospinal fluid (CSF), and/or tumor tissue as well as neuro-imaging to identify biomarkers predictive of response, recurrence, and resistance.
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 ≤18 years will start at the recommended phase 2 dose of 115 mg/m2/day and patients >18 years will start at 150mg/dose. All patients will be treated 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.
- Conditions
- High Grade Glioma, Diffuse Intrinsic Pontine Glioma, Anaplastic Astrocytoma, Infant Type Hemispheric Glioma, Glioblastoma, Glioblastoma Multiforme
- Being tested
- Lorlatinib, Lorlatinib with chemotherapy1, Lorlatinib with chemotherapy 2, Lorlatinib post Radiation
- Keywords
- ALK fusion, ROS fusion, High Grade Glioma, Diffuse Intrinsic Pontine Glioma
- Medical subject headings
- Glioma, Diffuse Intrinsic Pontine Glioma, Astrocytoma, Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LorlatinibDrug
Also called LOBRENA
Continue maintenance monotherapy for total 12 cycles
Lorlatinib with chemotherapy1Drug
Also called LOBRENA
Continue lorlatinib with BABY-POG chemotherapy backbone for 72 weeks
Lorlatinib with chemotherapy 2Drug
Also called LOBRENA
Continue lorlatinib with HIT-SKK chemotherapy backbone for 42 weeks
Lorlatinib post RadiationDrug
Also called LOBRENA
Continue lorlatinib monotherapy 28 days post completion of radiation therapy for 12 cycles
| Study group | Role | What they receive |
|---|---|---|
| Lorlatinib Monotherapy | Experimental | 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. Receives: Drug: Lorlatinib |
| Lorlatinib Combination with BABY POG chemotherapy | Experimental | 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 Receives: Drug: Lorlatinib; Drug: Lorlatinib with chemotherapy1 |
| Lorlatinib Combination with HIT-SKK chemotherapy | Experimental | 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. Receives: Drug: Lorlatinib; Drug: Lorlatinib with chemotherapy 2 |
| Lorlatinib Maintenance Therapy post RT | Experimental | 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 Receives: Drug: Lorlatinib; Drug: Lorlatinib post Radiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day 1 of 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
Measured: From Day 1 of protocol treatment through 30 days following end of protocol treatment
Secondary outcomes (4)
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.
Measured: 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.
Measured: Day 1 of 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.
Measured: 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
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.
Measured: From diagnosis through the end of follow-up period.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2024
- Study start3 Aug 2025
- Primary completion1 Jul 2029 (estimated)
- Study completion1 Jun 2035 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for High Grade GliomaStudies of the same condition, open and under way.
- More trials run by Nationwide Children's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Feasibility
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nationwide Children's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer
- Responsible party
- Sponsor
- Investigators
- Hamza Gorsi, MD, Study chair, Children's Hospital of MichiganSusan Chi, MD, Study chair, Dana-Farber Cancer InstituteMaryam Fouladi, MD, Principal investigator, Nationwide Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06333899
- Sponsor's protocol ID
- CONNECT TarGeT-L
- Other IDs
- R01FD008167
- Status last verified
- Jun 2026
- First submitted
- 14 Mar 2024
- Last updated
- 29 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06333899
- Acronym / sponsor ID
- CONNECT TarGeT-L
- Conditions
- High Grade Glioma, Diffuse Intrinsic Pontine Glioma, Anaplastic Astrocytoma, Infant Type Hemispheric Glioma, Glioblastoma, Glioblastoma Multiforme
- Keywords
- ALK fusion, ROS fusion, High Grade Glioma, Diffuse Intrinsic Pontine Glioma
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Nationwide Children's HospitalUniversity, hospital or other
- Collaborators
- Pfizer
- Study start
- 3 Aug 2025 (actual)
- Primary completion
- 1 Jul 2029 (estimated)
- Study completion
- 1 Jun 2035 (estimated)
- First posted
- 27 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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 of lorlatinib administered orally, once daily, at 115 mg/m2/day (or maximum of 200mg/dose) for pediatric patients, and 150mg/dose for patients >18 years, 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 after discussion with Study Chairs. 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.
This study will be a part of the TarGeT, molecularly-guided umbrealla trial in children, adolescents, and young adults newly diagnosed with HGG, including diffuse intrinsic pontine glioma (DIPG)/diffuse midline glioma (DMG). Patients will undergo (1) upfront comprehensive tumor molecular profiling using multi-omic approach with rapid return of results, (2) stratification to biologically-targeted treatment arms to assess treatment efficacy, and (3) longitudinal evaluation of peripheral blood, cerebrospinal fluid (CSF), and/or tumor tissue as well as neuro-imaging to identify biomarkers predictive of response, recurrence, and resistance.
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 ≤18 years will start at the recommended phase 2 dose of 115 mg/m2/day and patients >18 years will start at 150mg/dose. All patients will be treated 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- Feasibility
| Arm | Type | Receives |
|---|---|---|
| Lorlatinib Monotherapy | Experimental | Drug: LorlatinibLorlatinib 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. |
| Lorlatinib Combination with BABY POG chemotherapy | Experimental | Drug: Lorlatinib, Drug: Lorlatinib with chemotherapy1Lorlatinib 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 |
| Lorlatinib Combination with HIT-SKK chemotherapy | Experimental | Drug: Lorlatinib, Drug: Lorlatinib with chemotherapy 2Lorlatinib 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. |
| Lorlatinib Maintenance Therapy post RT | Experimental | Drug: Lorlatinib, Drug: Lorlatinib post RadiationLorlatinib 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 |
Who may qualify
- Ages
- 1 year to 21 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (19 listed)
- Patients must be ≥ 12 months and ≤ 21 years of age at the time of study enrollment on TarGeT-SCR.
- 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 2-4. All other HGGs must be Grade 3 or 4.
- Disease Status:
- Patients with disseminated DIPG or HGG are eligible only if the patient is to receive chemotherapy only, i.e. no craniospinal RT is intended to be given. MRI of spine must be performed if disseminated disease is suspected clinically by the treating physicians. Patients with primary spinal tumors are eligible only if the patient is to receive either chemotherapy or focal radiation therapy, i.e., no craniospinal RT is intended to be given. Patients with leptomeningeal disease only, with no definitive identifiable primary tumor, and documented ALK or ROS-1 fusion, must be discussed with the Study Chair on a case-by-case basis.
Key exclusion criteria (13 listed)
- Pregnant or breast-feeding women will not be entered on this study due to unknown risks of fetal and teratogenic adverse events as seen in animal/human studies. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
- Females of reproductive potential must use an effective non-hormonal method of contraception, since lorlatinib can render hormonal contraceptives ineffective, during study treatment and for at least 6 months after the final dose. Males with female partners of reproductive potential must use effective contraception during treatment with lorlatinib and for 3 months after the final dose.
- Concomitant Medications
- Infection: Patients must not have any active, uncontrolled systemic bacterial, viral or fungal infection.
- Patients who have received prior solid organ transplantation are not eligible.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LorlatinibAlso: LOBRENAContinue maintenance monotherapy for total 12 cycles | Drug | Lorlatinib Combination with BABY POG chemotherapy, Lorlatinib Combination with HIT-SKK chemotherapy, Lorlatinib Maintenance Therapy post RT, Lorlatinib Monotherapy |
| Lorlatinib with chemotherapy1Also: LOBRENAContinue lorlatinib with BABY-POG chemotherapy backbone for 72 weeks | Drug | Lorlatinib Combination with BABY POG chemotherapy |
| Lorlatinib with chemotherapy 2Also: LOBRENAContinue lorlatinib with HIT-SKK chemotherapy backbone for 42 weeks | Drug | Lorlatinib Combination with HIT-SKK chemotherapy |
| Lorlatinib post RadiationAlso: LOBRENAContinue lorlatinib monotherapy 28 days post completion of radiation therapy for 12 cycles | Drug | Lorlatinib Maintenance Therapy post RT |
Primary outcome
Disease Control Rate
Time frame: 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
Time frame: 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
4 secondary outcomes
Objective Response Rate (ORR) in HGG
Time frame: From Day 1 of protocol treatment through 30 days following end of protocol treatment
Overall Survival (OS) in HGG
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
Progression-Free Survival in HGG
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
Associations between genomic tumor alterations with radiographic response
Time frame: From diagnosis through the end of follow-up period.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jun 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
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
18 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Lorlatinib, Lorlatinib with chemotherapy1 and Lorlatinib with chemotherapy 2 in people with High Grade Glioma and Diffuse Intrinsic Pontine Glioma, run by Nationwide Children's Hospital at 18 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 29 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in United States, Australia, Canada, Germany, Netherlands and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kelsey H Troyer, PhD (16147223284, kelsey.troyer@nationwidechildrens.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease Control Rate (time frame: Day 1 of treatment until the end of cycle 2 (each cycle is 28 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jun 2026.