RecruitingRare disease

Study of Larotrectinib and Drug Combination for Children with Newly Diagnosed High-Grade Glioma with NTRK Fusion

Verified siteRegistered drug

Clinical Trials Concierge

Prefer not to search? Our Concierge searches the trials for you.

What is this trial about?

A plain-language summary of the goals, design and what participants do

This clinical trial is focused on studying a type of brain cancer called high-grade glioma, which includes a specific form known as diffuse intrinsic pontine glioma. These are aggressive brain tumors that occur in children. The study is investigating the use of a treatment called Larotrectinib, which is also known by its code name BAY2757556. Larotrectinib is designed to target a specific genetic change called NTRK fusion that can be present in these tumors. The treatment is available in different forms, including an oral solution and capsules.

The purpose of the study is to evaluate how well Larotrectinib can control the disease in young children with newly diagnosed high-grade glioma that has the NTRK fusion. The study will also look at the safety of using Larotrectinib alone and in combination with other chemotherapy drugs. These chemotherapy drugs include Carboplatin, Methotrexate, Vincristine sulfate, Cyclophosphamide monohydrate, and Etoposide phosphate. Some of these drugs are given through an injection into a vein, known as intravenous administration.

Participants in the study will receive Larotrectinib for a certain period, and their response to the treatment will be monitored. The study will also assess any side effects that may occur. The trial aims to provide valuable information on the effectiveness and safety of Larotrectinib for treating this type of brain cancer in children.

The research process

The trial runs in 6 steps – from screening to follow-up. Each step says what happens and what the team monitors.

Step 1
Enrollment
Upon joining the study, the patient must meet specific criteria, including age and organ function requirements. A written informed consent must be signed by the patient or their legal representative.
Step 2
Initial treatment phase
The patient will begin treatment with larotrectinib, administered as an oral solution. This phase involves two cycles of larotrectinib monotherapy to assess the disease control rate.
Step 3
Combination treatment phase
Following the initial treatment phase, larotrectinib will be combined with chemotherapy. The chemotherapy drugs include carboplatin, methotrexate, vincristine sulfate, cyclophosphamide monohydrate, and etoposide phosphate. These are administered intravenously.
Step 4
Post-radiation therapy
After focal radiation therapy, the patient will continue to receive larotrectinib to evaluate its safety and effectiveness in combination with the previous treatments.
Step 5
Monitoring and assessment
Throughout the trial, the patient's response to treatment will be monitored. This includes assessing the disease control rate and any treatment-related adverse events.
Step 6
Completion
The trial is expected to conclude by May 31, 2036. The patient's participation will end after the completion of the protocol treatment and a 30-day follow-up period.

Who can join the trial?

12 criteria

Patients must be **21 years old or younger** at the time of joining the study.
Patients must have **adequate neurologic function**. If they have a seizure disorder, they can join if they are taking medication for it and it is well controlled.
Patients and/or their parents or legal guardians must sign a **written informed consent**. This means they agree to participate after understanding the study details.
Patients must have a **newly diagnosed high-grade glioma (HGG)**, including a type called **diffuse intrinsic pontine glioma (DIPG)**. The tumor must have a specific change called **NTRK fusion**, confirmed by certain lab tests.
Patients with **disseminated DIPG or HGG** can join only if they will receive chemotherapy and not a type of radiation called craniospinal RT. An MRI of the spine is needed if the disease is suspected to have spread.
Patients with **primary spinal tumors** can join if they will receive either chemotherapy or focused radiation therapy, but not craniospinal RT.
Patients must have a **performance level** of at least 50% on a scale called Karnofsky (for those over 16) or Lansky (for those 16 and under). This means they can perform daily activities to some extent.
Patients must not have received any previous **anti-cancer chemotherapy**. However, they can have used **corticosteroids** before.
Patients must have **adequate bone marrow function**, which includes having enough white blood cells, platelets, and hemoglobin.
Patients must have **adequate kidney function**, shown by normal levels of a substance called creatinine or a test called creatinine clearance.
Patients must have **adequate liver function**, with certain liver tests within normal limits.
Patients must have **adequate lung function**, with oxygen levels above 94% when breathing room air, if needed.

Who cannot join the trial?

7 criteria

Patients who have not been newly diagnosed with a **high grade glioma (HGG)**, which is a type of brain tumor.
Patients who do not have a specific type of HGG called **diffuse intrinsic pontine glioma (DIPG)**, which is a tumor located in a part of the brainstem.
Patients who do not have a genetic change known as **NTRK fusion**, which is a specific alteration in the genes that can affect tumor growth.
Patients who are not within the age range specified for the study, which is typically young children.
Patients who are not able to safely receive the study medication, **larotrectinib**, either alone or in combination with chemotherapy.
Patients who have not completed **focal radiation therapy**, which is a treatment that targets a specific area of the brain.
Patients who are not able to participate in the study due to other health conditions or factors that make it unsafe for them.

Clinical Trials Concierge

Prefer not to search? Our Concierge searches the trials for you.

Tell us about your condition – we search every trial in Europe and connect you with the right site.

We usually reply within a few days

Verified sites

All sites with verified contact details – recruitment status may not be available; ask directly

Verified
Charite Universitaetsmedizin Berlin KöR
Berlin, Germany
Verified
Universitaetsklinikum Augsburg
Augsburg, Germany
Verified
Universitaetsklinikum Heidelberg AöR
Heidelberg, Germany

Trial locations

Where you can join this trial

Countries are shaded by recruitment status. Click a recruiting country to ask about joining there.

Recruiting

Not finding your country?

Not sure what to do next?

Joining a clinical trial can seem overwhelming. We guide you step by step, so you know exactly what to expect and how we support you through the process.

See the full process and FAQ

Investigated drugs

Larotrectinib is a medication being studied for its ability to control disease in young children with newly diagnosed high-grade glioma that has a specific genetic feature called NTRK fusion. The trial aims to see how well the medication works on its own after two treatment cycles. Additionally, the study is looking at how safe and feasible it is to use larotrectinib in combination with chemotherapy, as well as its safety when given after targeted radiation therapy.

What is already known about the treatment

Larotrectinib – Larotrectinib is administered orally and is currently being studied in clinical trials for its effectiveness in treating children with newly diagnosed high-grade glioma, including diffuse intrinsic pontine glioma, that have NTRK gene fusions. It is an approved medication in some contexts and is being further evaluated for its safety and efficacy in combination with chemotherapy and post-radiation therapy. The main therapeutic indication for larotrectinib is tumors with NTRK gene fusions, which are rare but can occur in various types of cancer. At the molecular level, larotrectinib works by inhibiting the TRK proteins, which are involved in the growth and survival of cancer cells. It is classified as a targeted cancer therapy, specifically a TRK inhibitor.

Investigated diseases

High Grade Glioma (HGG)
This is a type of aggressive brain tumor that originates from glial cells, which support and protect nerve cells in the brain. It is characterized by rapid growth and a tendency to infiltrate surrounding brain tissue, making it challenging to manage. Symptoms can vary depending on the tumor's location but often include headaches, seizures, and neurological deficits. HGG is known for its high cellularity and abnormal blood vessel formation. It can occur in both children and adults, with varying subtypes based on genetic and molecular features.
Diffuse Intrinsic Pontine Glioma (DIPG)
This is a rare and aggressive brain tumor that primarily affects children, occurring in the pons region of the brainstem. It is characterized by its diffuse growth pattern, which means it spreads widely throughout the brain tissue, making surgical removal impossible. Symptoms often include problems with balance and coordination, facial weakness, and difficulty with eye movements. DIPG progresses rapidly, leading to worsening neurological function over time. The tumor's location in the brainstem affects vital functions, contributing to its complexity.