A Pilot Study of Larotrectinib for Newly-Diagnosed High-Grade Glioma With NTRK Fusion (NCT04655404)

🧪 Interventions in This Study

• Larotrectinib (DRUG)

Check every box below. If you can check all of them, you may meet the study's basic screening requirements (final eligibility is confirmed by the site team).

1. Age: Patients ≤ 21 years of age (birth to 21 years of age) at the time of study enrollment will be eligible.
2. 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.
3. 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.
4. 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.
5. 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.
6. Prior Therapy: Patients must not have received any prior anti-cancer chemotherapy. Prior use of corticosteroids are allowed (see below Exclusion Criteria)
7. 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.

🔍 Extracted verbatim from the official NIH eligibility criteria. Always confirm with the study coordinator.

📍 All Participating Trial Locations (21 Sites)

• Children's Hospital Colorado — Aurora, Colorado
• Children's National Medical Center — Washington D.C., District of Columbia
• Ann & Robert H. Lurie Children's Hospital of Chicago — Chicago, Illinois
• Dana-Farber Cancer Institute — Boston, Massachusetts
• Duke University Health System — Durham, North Carolina
• Cincinnati Children's Hospital Medical Center — Cincinnati, Ohio
• Nationwide Children's Hospital — Columbus, Ohio
• Children's Hospital of Philadelphia — Philadelphia, Pennsylvania
• Texas Children's Hospital — Houston, Texas
• Seattle Children's Hospital — Seattle, Washington
• Sydney Children's Hospital — Randwick, New South Wales
• Queensland Children's Hospital — South Brisbane, Queensland
• Perth Children's Hospital — Perth, Western Australia
• The Hospital for Sick Children (SickKids) — Toronto, Ontario
• Montreal Children's Hospital — Montreal, Quebec
• Hopp Children's Cancer Center at NCT Heidelberg (KiTZ) — Heidelberg, Baden-Wurttemberg
• University Medical Center Augsburg — Augsburg,
• University Hospital Berlin — Berlin,
• University Hospital Koln — Cologne,
• University Medical Center Gottingen — Göttingen,
• Starship Children's Hospital — Auckland, Grafton

📞 Contact the Study Coordinator

Phone: (614) 722-3284

Email: kelsey.troyer@nationwidechildrens.org

Coordinator details come directly from the registered NIH protocol. Confirm the study is still recruiting before traveling.

💰 Cost, Insurance & Patient Rights

• 100% Free Items: The investigational treatment and protocol-required procedures are supplied at zero cost by the sponsor.
• Routine Patient Care: Under federal law (ACA § 2709) and many state statutes, routine care costs are covered during participation.
• Voluntary Participation: You may withdraw at any time without affecting your standard medical care.

More studies in High Grade Glioma

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• Lutathera for Treatment of Recurrent or Progressive High-Grade CNS Tumors — Aurora, Colorado
• MRI in High-Grade Glioma Patients Undergoing Chemoradiation — Winston-Salem, North Carolina
• Lorlatinib for Newly-Diagnosed High-Grade Glioma With ROS or ALK Fusion — Aurora, Colorado
• A Pilot Study Investigating Upfront Adaptive Immunotherapy Approach in Children, Adolescent and Young Adult (CAYA) Patients With Replication-Repair Deficient (RRD) High-Grade Gliomas (HGG) — Toronto, Ontario

Explore by condition: All High Grade Glioma clinical trials

💡 How to Participate

1. Check the checklist above to see if you may qualify.
2. Contact the study coordinator using the phone/email above.
3. Ask about the visit schedule, what is covered at no cost, and any travel support.
4. Confirm with your own doctor before making a decision.