Entrectinib for Brain Tumors
What You Need to Know Before You Apply
What is the purpose of this trial?
This trial explores the effectiveness of the drug entrectinib (Rozlytrek) in treating young children with specific brain tumors. It targets children under 3 years old with high-grade glioma or other central nervous system tumors that have genetic changes known as NTRK or ROS1 fusions. Families with newly diagnosed children who have not started other treatments might consider this trial. The researchers aim to determine if entrectinib can effectively manage these challenging tumors. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, contributing to important early findings.
Do I need to stop my current medications to join the trial?
The trial requires that participants not be on enzyme-inducing antiepileptic drugs (EIAEDs) and not have had any prior cancer therapy, including chemotherapy, targeted therapy, immunotherapy, cellular therapy, or radiation. If you are on these medications, you may need to stop them to participate.
Is there any evidence suggesting that entrectinib is likely to be safe for young children with brain tumors?
Research has shown that entrectinib is generally safe and well-tolerated. It works effectively in children with tumors caused by changes in specific genes, such as NTRK or ROS1, which can lead to cancer. Entrectinib has undergone testing in several studies, and results suggest it acts quickly and effectively.
Safety data from these studies indicate that while side effects can occur, they are usually manageable. Doctors know how to treat them if they happen. Possible side effects include fatigue, dizziness, or changes in taste, but these can vary from person to person.
The FDA has already approved entrectinib for treating certain cancers in adults, indicating its safety is well-understood. However, individual reactions may vary, so discussing potential risks with a healthcare provider before joining a trial is important.12345Why do researchers think this study treatment might be promising for brain tumors?
Entrectinib is unique because it specifically targets genetic mutations found in certain brain tumors, namely NTRK1/2/3 and ROS1 fusions. Unlike traditional treatments such as chemotherapy and radiation, which generally attack rapidly dividing cells, entrectinib works by directly inhibiting these specific genetic drivers of tumor growth. Researchers are excited about entrectinib because it offers a more targeted approach, potentially leading to more effective treatment with fewer side effects for young patients with these particular genetic profiles.
What evidence suggests that entrectinib might be an effective treatment for brain tumors?
Studies have shown that entrectinib can cause strong and lasting effects in children with tumors that have NTRK or ROS1 gene fusions. Reports from combined trials indicated a 57.7% success rate for entrectinib in shrinking or stopping the growth of solid tumors, including brain tumors, in young patients. This means it can help reduce tumor size or prevent growth. Entrectinib targets specific proteins made by these gene fusions, which helps stop tumor growth. In this trial, participants in Cohort 1, younger than 3 years with NTRK1/2/3- or ROS1-fused high-grade glioma, and participants in Cohort 2, younger than 3 years with NTRK1/2/3- or ROS1-fused CNS tumors other than high-grade glioma, will receive entrectinib therapy. These findings support entrectinib's potential to effectively treat high-grade glioma and other central nervous system (CNS) tumors in young children.12356
Who Is on the Research Team?
Daniel Moreira, MD, MEd
Principal Investigator
St. Jude Children's Research Hospital
Are You a Good Fit for This Trial?
This trial is for children under 3 with high-grade glioma or other CNS tumors that have specific genetic markers (NTRK1/2/3 or ROS1). To join, they must not have had previous treatments and should be able to undergo MRI scans. Children with certain health conditions or taking drugs that interfere with entrectinib are excluded.Inclusion Criteria
Exclusion Criteria
Timeline for a Trial Participant
Screening
Participants are screened for eligibility to participate in the trial
Treatment
Participants receive entrectinib enterally once daily on days 1-28 of each cycle. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.
Surgical Intervention
A gross total resection or significant debulking may become possible if a response to entrectinib is seen. If surgical resection is performed and a gross total resection is achieved, 24 cycles of entrectinib will be completed, including those before and after surgery.
Follow-up
Participants are monitored for safety and effectiveness after treatment. Follow-up continues for 5 years to assess long-term outcomes such as progression-free survival and overall survival.
What Are the Treatments Tested in This Trial?
Interventions
- Entrectinib
Entrectinib is already approved in United States, European Union, Japan for the following indications:
- Metastatic non-small cell lung cancer (mNSCLC) with a neurotrophic receptor tyrosine kinase (NTRK) gene fusion
- Solid tumors with a NTRK gene fusion
- Solid tumours with a NTRK gene fusion
- Metastatic non-small cell lung cancer (NSCLC) with a NTRK gene fusion
- Solid tumours with a NTRK gene fusion
Find a Clinic Near You
Who Is Running the Clinical Trial?
St. Jude Children's Research Hospital
Lead Sponsor
Hoffmann-La Roche
Industry Sponsor
Dr. Levi Garraway
Hoffmann-La Roche
Chief Medical Officer since 2019
MD from the University of Basel
Dr. Thomas Schinecker
Hoffmann-La Roche
Chief Executive Officer since 2023
PhD in Molecular Biology from New York University