High Grade GliomaEarly Phase 1NCT04655404
A Pilot Study of Larotrectinib for Newly-Diagnosed High-Grade Glioma With NTRK Fusion
A Early Phase 1 study testing Larotrectinib and Larotrectinib surgical in people with High Grade Glioma and Diffuse Intrinsic Pontine Glioma, run by Nationwide Children's Hospital at 21 sites in 5 countries.
Trial summary
This is a pilot study that will evaluate disease status in children that have been newly diagnosed high-grade glioma with TRK fusion. The evaluation will occur after 2 cycles of the medication (Larotrectinib) have been given. Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- High Grade Glioma, Diffuse Intrinsic Pontine Glioma
- What is being tested?
- Larotrectinib and Larotrectinib surgical
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 21 sitesin 5 countries
- Study dates
- 8 Apr 2021to 1 Dec 2036
- 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 Up to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age: Patients ≤ 21 years of age (birth to 21 years of age) at the time of study enrollment will be eligible.
- Diagnosis: Patients with newly-diagnosed high-grade (HGG), including diffuse intrinsic pontine gliomas (DIPG), whose tumors are documented in a CLIA/CAP certified lab (or clinically equivalent method considered standard in non-US sites) to harbor an NTRK fusion alteration by FISH, PCR, or next generation sequencing are eligible. Patients must have had histologically verified high-grade glioma such as anaplastic astrocytoma, glioblastoma, or H3 K27-mutant diffuse midline glioma verified at a CONNECT site.
- For sites that do not have CLIA-certified equivalent (certified laboratory) to assess NTRK fusion, testing will be conducted centrally at NCH. NTRK testing will be performed by NGS using targeted RNA-sequencing (Archer Solid Tumor analysis) Please submit 10 unstained sections on charged slides at 10uM thickness, or 10 scrolls cut at 10uM thickness, along with submission of an H\&E slide. Formalin-fixed paraffin embedded (FFPE) tissue block and FFPE tissue scroll specimens must contain minimum of 25% tumor Snap-frozen tissue specimens are also acceptable and they must contain a minimum of 10% tumor. Please note that turn-around time for this test is up to 21 days.
- 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 NTRK fusion, must be discussed with the Study Chair on a case-by-case basis.
- Surgical Cohort ONLY: Patients with newly-diagnosed HGG with NTRK fusions who have undergone prior biopsy and for whom further resection is indicated for a more definitive surgery at an enrolling site will be eligible to enroll onto the surgical study. DIPG patients are not eligible for the surgical cohort.
- Performance Level: 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.
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- Prior Therapy: Patients must not have received any prior anti-cancer chemotherapy. Prior use of corticosteroids are allowed (see below Exclusion Criteria)
- Organ Function Requirements: Adequate Bone Marrow Function Defined as:
- Peripheral absolute neutrophil count (ANC) ≥ 1000/mm3 Platelet count ≥ 100,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) Hemoglobin >8 g/dL (may receive transfusions)
- Adequate Renal Function Defined as: Serum creatinine within normal institutional limits, or Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2
- Adequate Liver Function Defined as: Total bilirubin ≤ 2.5 × institutional upper limit of normal AST(SGOT)/ALT(SGPT) ≤ 2.5 × institutional upper limit of normal
- Adequate Pulmonary Function Defined as: Pulse oximetry > 94% on room air if there is clinical indication for determination (e.g. dyspnea at rest).
- Adequate Neurologic Function Defined as: Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled. See Section 5.5.2 and Appendix III for EIAED guidelines.
- 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
- Pregnancy or Breast-Feeding: 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.
- Concomitant Medications Investigational 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.
- 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. (See Appendix III.) Strong inducers or inhibitors of CYP3A4 should be avoided from 7 days prior to enrollment to the end of the study.
- 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.
Trial locations and contacts
21 sites in 5 countries. Contact the study team or a site near you to ask about taking part.
21 sites in 5 countries
United States10 sites, 9 recruiting
- Recruiting
Children's Hospital Colorado
Aurora, Colorado, 80045
Holly Lindsay, MD, 720-777-8314, holly.lindsay@childrenscolorado.org
- Recruiting
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Susan Chi, MD, 617-632-4386, Susan_chi@dfci.harvard.edu
- Withdrawn
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
- Recruiting
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Peter de Blank, MD, 513-517-2068, Peter.deBlank@cchmc.org
- Recruiting
Nationwide Children's Hospital
Columbus, Ohio, 43235
Maryam Fouladi, MD, 6147225758, Maryam.fouladi@nationwidechildrens.org
Maryam Fouladi, MD
- Recruiting
Duke University Health System
Durham, North Carolina, 27708
Daniel Landi, MD, 919-684-5013, pedsneuronc@duke.edu
- Recruiting
Texas Children's Hospital
Houston, Texas, 77030
Patricia Baxter, MD, 832-824-4681, pabaxter@txch.org
- Recruiting
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Michael J Fisher, MD, 215-590-5188, fisherm@email.chop.edu
- Recruiting
Seattle Children's Hospital
Seattle, Washington, 98105
Sarah Leary, MD, 206-987-2106, sarah.leary@seattlechildrens.org
- Recruiting
Children's National Medical Center
Washington D.C., District of Columbia, 20010
Eugene Hwang, MD, 202-476-5046, ehwang@childrensnational.org
Germany5 sites, 5 recruiting
- Recruiting
University Medical Center Augsburg
Augsburg
Michael Fruhwald, MD, michael.fruehwald@uk-augsburg.de
- Recruiting
University Hospital Berlin
Berlin
Pablo Hernaiz Driever, MD, pablo.hernaiz@charite.de
- Recruiting
University Hospital Koln
Cologne
Matthias Fischer, MD, matthias.fischer@uk-koeln.de
- Recruiting
University Medical Center Gottingen
Göttingen
C. Kramm, MD, 0551 3962005
- Recruiting
Hopp Children's Cancer Center at NCT Heidelberg (KiTZ)
Heidelberg, Baden-Wurttemberg, 69120
Olaf Witt, MD, 49 6221 42 3570, o.witt@kitz-heidelberg.de
Australia3 sites, 3 recruiting
- Recruiting
Perth Children's Hospital
Perth, Western Australia, 6000
Nick Gottardo, MBChB, 618 6456 0241, nick.gottardo@health.wa.gov.au
- Recruiting
Sydney Children's Hospital
Randwick, New South Wales, 2031
David Ziegler, MBBS, 612 9382 1730, d.ziegler@unsw.edu.au
- Recruiting
Queensland Children's Hospital
South Brisbane, Queensland, 4101
Tim Hassall, MBBS, 61 7 3068 3593, tim.hassall@health.qld.gov.au
Canada2 sites, 2 recruiting
- Recruiting
Montreal Children's Hospital
Montreal, Quebec, H4A3J1
Genevieve Legault, MD, 514-412-4400 ext. 60497, Genevieve.legault4@mcgill.ca
- Recruiting
The Hospital for Sick Children (SickKids)
Toronto, Ontario, M5G1X8
Eric Bouffet, MD, 416-813-7457, eric.bouffet@sickkids.ca
New Zealand1 site, 1 recruiting
- 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 and Surgical Study of Larotrectinib for Treatment of Children With Newly-Diagnosed High-Grade Glioma With NTRK Fusion
This is a pilot study that will evaluate disease status in children that have been newly diagnosed high-grade glioma with TRK fusion. The evaluation will occur after 2 cycles of the medication (Larotrectinib) have been given.
The study will also evaluate the safety of larotrectinib when given with chemotherapy in your children; as well as the safety larotrectinib when given post-focal radiation therapy.
Read the detailed description
In this pilot study, we will assess the disease control rate (Continued Complete Response-CCR, Complete Response-CR, Partial Response-PR and Stable Disease-SD) as well as survival rate (overall survival- OS and progression free survival- PFS) in children with newly diagnosed HGG with TRK fusion who receive 2 cycles of larotrectinib monotherapy administered orally, twice daily, at 100 mg/m2 continuously on a 28-day cycle schedule. After 2 monotherapy cycles of larotrectinib, patients with CCR or CR will continue to receive larotrectinib maintenance therapy as monotherapy for a total of 12 cycles. Continuation of treatment beyond 12 cycles, and up to 24 cycles, may be considered for patients on Larotrectinib monotherapy if they are receiving clinical benefit from the study, at the discretion of the treating physician.
Patients ≤ 48 months with PR or SD after 2 cycles of larotrectinib will go on to receive combination therapy with standard backbone chemotherapy (BABYPOG or HIT-SKK). Patients > 48 months of age (or patients ≥ 36 months of age, or patients with DIPG >18 months of age, at the discretion of the local investigator) will receive focal radiation therapy. A surgical cohort study will be explored whereby patients who have had a tumor biopsy/partial resection at their local institution and are planned to subsequently undergo definitive resection will receive 3-5 days (6-10 doses) of larotrectinib pre-surgery.
The study design of this trial requires 15 patients evaluable for disease control and for safety/ toxicity of larotrectinib as monotherapy. The surgical cohort will enroll up to 4 patients and will count towards the total 15 evaluable patients. A minimum of 6 patients will be evaluable for safety toxicity of larotrectinib in combination with standard-of-care chemotherapy or radiotherapy.
- Being tested
- Larotrectinib, Larotrectinib surgical
- Keywords
- NTRK gene fusion, BABYPOG, HIT-SKK, Larotrectinib
- Medical subject headings
- Glioma, Diffuse Intrinsic Pontine Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LarotrectinibDrug
- Larotrectinib monotherapy x2 cycles followed by disease evaluation
- Larotrectinib with or without chemotherapy backbone
Larotrectinib surgicalProcedure or surgery
- Surgical cohort: Larotrectinib x 3-5 days prior to definitive surgery followed by Larotrectinib monotherapy x2 cycles followed by disease evaluation
- Larotrectinib with or without chemotherapy backbone
| Study group | Role | What they receive |
|---|---|---|
| Feasibility Cohort | Experimental | Larotrectinib administered PO, BID @100 mg/m2 on a 28-day cycle schedule. Receives: Drug: Larotrectinib |
| Surgical Cohort | Experimental | Larotrectinib administered PO, BID @100 mg/m2 3-5 days prior to definitive surgery, followed by Larotrectinib administered PO, BID @100 mg/m2 on a 28-day cycle schedule. Receives: Drug: Larotrectinib; Procedure: Larotrectinib surgical |
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 larotrectinib in young children newly diagnosed with HGG carrying NTRK fusion after 2 cycles of larotrectinib monotherapy.
Measured: At the end of Cycle 2 (each cycle is 28 days)
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
To assess the safety and tolerability of larotrectinib given in combination with chemotherapy or post-focal radiation therapy in young children newly diagnosed with HGG carrying NTRK fusion. This will be achieved by calculating the number of participants with, as well as frequency and severity of, larotrectinib-related Adverse Events as assessed by CTCAE v5.0.
Measured: From Day 1 of treatment through 30 days following end of protocol treatment
Maximum Plasma Concentration [Cmax] of larotrectinib
To characterize the plasma pharmacokinetics (PK) of larotrectinib in children newly diagnosed with HGG carrying NTRK fusions who undergo a second definitive resection. This will be achieved by measuring the Maximum Plasma Concentration (Cmax) of larotrectinib in blood (plasma) samples collected at pre-dose (day -5), pre-surgery (day -1) and during surgery.
Measured: Days 1 through 5 of surgical cycle
Tumor Concentration of larotrectinib
To characterize the tumor pharmacokinetics (PK) of larotrectinib in children newly diagnosed with HGG carrying NTRK fusions who undergo a second definitive resection by measuring the concentration of larotrectinib in tumor tissue collected on day 5 of surgical cycle
Measured: Day 5 of surgical surgical cycle
Secondary outcomes (2)
Objective response rate (ORR)
To assess the objective response rate (ORR) (Complete Response [CR] and Partial Response [PR]) of larotrectinib in children newly-diagnosed with HGG carrying NTRK fusion after 2 cycles of larotrectinib monotherapy.
Measured: At the end of Cycle 2 (each cycle is 28 days)
Survival rate
To assess overall (OS) and progression-free survivals (PFS) of children newly diagnosed with HGG carrying NTRK fusion treated with a larotrectinib-containing regimen at 1, 3 and 5 years and compared to historical data from BABYPOG and HIT-SKK.
Measured: From date of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Dec 2020
- Study start8 Apr 2021
- Primary completion1 Dec 2026 (estimated)
- Study completion1 Dec 2036 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- Single group
- Model description
- Feasibility and surgical cohorts
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nationwide Children's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Susan Chi, MD, Study chair, Dana Farber/ Boston Children's Cancer and Blood Disorders CenterMaryam Fouladi, MD, Study chair, Nationwide Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04655404
- Sponsor's protocol ID
- CONNECT1903
- Status last verified
- Mar 2026
- First submitted
- 9 Nov 2020
- Last updated
- 18 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Bagchi A, Chiang J, Pinto S, Dhanda S, Gajjar A. Infant-Type Hemispheric Gliomas: A Review of Clinical, Radiologic, Histopathologic, and Molecular Features. J Natl Compr Canc Netw. 2025 Nov;23(11):e257064. doi: 10.6004/jnccn.2025.7064.
PubMed 41213248
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot and Surgical Study of Larotrectinib for Treatment of Children With Newly-Diagnosed High-Grade Glioma With NTRK Fusion
- ClinicalTrials.gov ID
- NCT04655404
- Acronym / sponsor ID
- CONNECT1903
- Keywords
- NTRK gene fusion, BABYPOG, HIT-SKK, Larotrectinib
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Nationwide Children's HospitalUniversity, hospital or other
- Study start
- 8 Apr 2021 (actual)
- Primary completion
- 1 Dec 2026 (estimated)
- Study completion
- 1 Dec 2036 (estimated)
- First posted
- 7 Dec 2020 (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.
This is a pilot study that will evaluate disease status in children that have been newly diagnosed high-grade glioma with TRK fusion. The evaluation will occur after 2 cycles of the medication (Larotrectinib) have been given.
The study will also evaluate the safety of larotrectinib when given with chemotherapy in your children; as well as the safety larotrectinib when given post-focal radiation therapy.
Detailed description
In this pilot study, we will assess the disease control rate (Continued Complete Response-CCR, Complete Response-CR, Partial Response-PR and Stable Disease-SD) as well as survival rate (overall survival- OS and progression free survival- PFS) in children with newly diagnosed HGG with TRK fusion who receive 2 cycles of larotrectinib monotherapy administered orally, twice daily, at 100 mg/m2 continuously on a 28-day cycle schedule. After 2 monotherapy cycles of larotrectinib, patients with CCR or CR will continue to receive larotrectinib maintenance therapy as monotherapy for a total of 12 cycles. Continuation of treatment beyond 12 cycles, and up to 24 cycles, may be considered for patients on Larotrectinib monotherapy if they are receiving clinical benefit from the study, at the discretion of the treating physician.
Patients ≤ 48 months with PR or SD after 2 cycles of larotrectinib will go on to receive combination therapy with standard backbone chemotherapy (BABYPOG or HIT-SKK). Patients > 48 months of age (or patients ≥ 36 months of age, or patients with DIPG >18 months of age, at the discretion of the local investigator) will receive focal radiation therapy. A surgical cohort study will be explored whereby patients who have had a tumor biopsy/partial resection at their local institution and are planned to subsequently undergo definitive resection will receive 3-5 days (6-10 doses) of larotrectinib pre-surgery.
The study design of this trial requires 15 patients evaluable for disease control and for safety/ toxicity of larotrectinib as monotherapy. The surgical cohort will enroll up to 4 patients and will count towards the total 15 evaluable patients. A minimum of 6 patients will be evaluable for safety toxicity of larotrectinib in combination with standard-of-care chemotherapy or radiotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Feasibility and surgical cohorts
| Arm | Type | Receives |
|---|---|---|
| Feasibility Cohort | Experimental | Drug: LarotrectinibLarotrectinib administered PO, BID @100 mg/m2 on a 28-day cycle schedule. |
| Surgical Cohort | Experimental | Drug: Larotrectinib, Procedure: Larotrectinib surgicalLarotrectinib administered PO, BID @100 mg/m2 3-5 days prior to definitive surgery, followed by Larotrectinib administered PO, BID @100 mg/m2 on a 28-day cycle schedule. |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (14 listed)
- Age: Patients ≤ 21 years of age (birth to 21 years of age) at the time of study enrollment will be eligible.
- Diagnosis: Patients with newly-diagnosed high-grade (HGG), including diffuse intrinsic pontine gliomas (DIPG), whose tumors are documented in a CLIA/CAP certified lab (or clinically equivalent method considered standard in non-US sites) to harbor an NTRK fusion alteration by FISH, PCR, or next generation sequencing are eligible. Patients must have had histologically verified high-grade glioma such as anaplastic astrocytoma, glioblastoma, or H3 K27-mutant diffuse midline glioma verified at a CONNECT site.
- For sites that do not have CLIA-certified equivalent (certified laboratory) to assess NTRK fusion, testing will be conducted centrally at NCH. NTRK testing will be performed by NGS using targeted RNA-sequencing (Archer Solid Tumor analysis) Please submit 10 unstained sections on charged slides at 10uM thickness, or 10 scrolls cut at 10uM thickness, along with submission of an H\&E slide. Formalin-fixed paraffin embedded (FFPE) tissue block and FFPE tissue scroll specimens must contain minimum of 25% tumor Snap-frozen tissue specimens are also acceptable and they must contain a minimum of 10% tumor. Please note that turn-around time for this test is up to 21 days.
- 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 NTRK fusion, must be discussed with the Study Chair on a case-by-case basis.
- Surgical Cohort ONLY: Patients with newly-diagnosed HGG with NTRK fusions who have undergone prior biopsy and for whom further resection is indicated for a more definitive surgery at an enrolling site will be eligible to enroll onto the surgical study. DIPG patients are not eligible for the surgical cohort.
Key exclusion criteria (8 listed)
- Pregnancy or Breast-Feeding: 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.
- Concomitant Medications Investigational 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.
- 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 |
|---|---|---|
| Larotrectinib1. Larotrectinib monotherapy x2 cycles followed by disease evaluation 2. Larotrectinib with or without chemotherapy backbone | Drug | Feasibility Cohort, Surgical Cohort |
| Larotrectinib surgical1. Surgical cohort: Larotrectinib x 3-5 days prior to definitive surgery followed by Larotrectinib monotherapy x2 cycles followed by disease evaluation 2. Larotrectinib with or without chemotherapy backbone | Procedure or surgery | Surgical Cohort |
Primary outcome
Disease control rate
Time frame: At 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 larotrectinib in young children newly diagnosed with HGG carrying NTRK fusion after 2 cycles of larotrectinib monotherapy.
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Time frame: From Day 1 of treatment through 30 days following end of protocol treatment
To assess the safety and tolerability of larotrectinib given in combination with chemotherapy or post-focal radiation therapy in young children newly diagnosed with HGG carrying NTRK fusion. This will be achieved by calculating the number of participants with, as well as frequency and severity of, larotrectinib-related Adverse Events as assessed by CTCAE v5.0.
Maximum Plasma Concentration [Cmax] of larotrectinib
Time frame: Days 1 through 5 of surgical cycle
To characterize the plasma pharmacokinetics (PK) of larotrectinib in children newly diagnosed with HGG carrying NTRK fusions who undergo a second definitive resection. This will be achieved by measuring the Maximum Plasma Concentration (Cmax) of larotrectinib in blood (plasma) samples collected at pre-dose (day -5), pre-surgery (day -1) and during surgery.
Tumor Concentration of larotrectinib
Time frame: Day 5 of surgical surgical cycle
To characterize the tumor pharmacokinetics (PK) of larotrectinib in children newly diagnosed with HGG carrying NTRK fusions who undergo a second definitive resection by measuring the concentration of larotrectinib in tumor tissue collected on day 5 of surgical cycle
2 secondary outcomes
Objective response rate (ORR)
Time frame: At the end of Cycle 2 (each cycle is 28 days)
Survival rate
Time frame: From date of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
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 18 Mar 2026.
- Derived from this study: PubMed 41213248Bagchi A, Chiang J, Pinto S, Dhanda S, Gajjar A. Infant-Type Hemispheric Gliomas: A Review of Clinical, Radiologic, Histopathologic, and Molecular Features. J Natl Compr Canc Netw. 2025 Nov;23(11):e257064. doi: 10.6004/jnccn.2025.7064.
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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.
Susan Chi, MD study chair
Dana Farber/ Boston Children's Cancer and Blood Disorders Center
Maryam Fouladi, MD study chair
Nationwide Children's Hospital
21 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Larotrectinib and Larotrectinib surgical in people with High Grade Glioma and Diffuse Intrinsic Pontine Glioma, run by Nationwide Children's Hospital at 21 sites in 5 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 14 inclusion and 8 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 18 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in United States, Germany, Australia, Canada, New Zealand. 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: At the end of Cycle 2 (each cycle is 28 days)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04655404, which also lists 1 linked publication.
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 18 Mar 2026.