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Larotrectinib for Newly-Diagnosed High-Grade Glioma with NTRK Fusion

This pilot study is looking at a medication called larotrectinib for children and young adults (up to 21 years old) who have been newly diagnosed with a type of brain tumor called high-grade glioma (HGG), including diffuse intrinsic pontine glioma (DIPG). To join, your tumor must have a specific genetic change called an NTRK fusion. The study will first give larotrectinib alone for two cycles (each cycle is 28 days) to see how well it controls the disease. It will also look at the safety of larotrectinib, both on its own and when given with chemotherapy or after radiation therapy. The main goals are to see how many participants' tumors shrink or stay stable, and to track any side effects.

Study design
This is a pilot study, meaning it's an early look at the treatment. It plans to enroll 15 participants and is an interventional study, meaning participants will receive a specific treatment.
What's involved
Participants will receive larotrectinib, either alone or with other treatments. Disease will be evaluated after two cycles (56 days) of treatment. Some participants may continue treatment for up to 24 cycles.
Compensation
Not stated in the trial record.
Follow-up
The number of participants with treatment-related side effects will be tracked for 30 days after the end of protocol treatment.

AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.

NCT04655404

A Pilot Study of Larotrectinib for Newly-Diagnosed High-Grade Glioma With NTRK Fusion

Recruiting
EARLY_PHASE1Up to 21InterventionalTreatment
Nationwide Children's Hospital
~15 participants
Updated 2026-03-18 on ClinicalTrials.gov
What's tested:LarotrectinibLarotrectinib surgical

At a glance

Recruiting sites
20 of 21 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Disease control rate
Measured over At the end of Cycle 2 (each cycle is 28 days)
+3 more outcomes measured

Conditions

High Grade Glioma
Diffuse Intrinsic Pontine Glioma

Explore related trials

Diffuse Intrinsic Pontine GliomaMalignant GliomaNTRK Family Gene

Where it's being run

21 sites across 17 states
Germany4
Ohio2
Colorado1
District of Columbia1
Illinois1
Massachusetts1
North Carolina1
Pennsylvania1

Study leadership

  • Susan Chi, MD · STUDY_CHAIR · Dana Farber/ Boston Children's Cancer and Blood Disorders Center
  • Maryam Fouladi, MD · STUDY_CHAIR · Nationwide Children's Hospital

Who to contact

Kelsey H Troyer, PhD
[email protected]
16147223284
Email the study team

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Eligibility criteria

Inclusion

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.
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.

Exclusion

Organ Function Requirements: Adequate Bone Marrow Function Defined as:
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.
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.

What this trial measures

  • Disease control rateAt 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 v5.0From 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 larotrectinibDays 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 larotrectinibDay 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