Entrectinib as a Single Agent in Upfront Therapy for Children <3 Years of Age With NTRK1/2/3 or ROS1-FUSED CNS Tumors

NCT06528691 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: GLOBOTRKNCI-2024-02977
• Study Type: interventional
• Target: 52
• Locations: 3 countries
• Sites: 4

Brief Summary

This clinical trial tests how well entrectinib works to treat patients less than 3 years of age with NTRK 1/2/3 or ROS1 fused, high grade glioma or other central nervous system (CNS) tumors.

Conditions

CNS Tumor; High Grade Glioma

Keywords

CNS Tumors; High Grade Glioma with NTRK1/2/3 gene fusion; High Grade Glioma with ROS1 gene fusion; CNS tumor other than HGG harboring NTRK1/2/3 gene fusion; CNS tumor other than HGG harboring ROS1 gene fusion; Children

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR) (Cohort 1)

  ORR is defined as the percentage of patients with either partial or complete response assessed at the protocol-defined evaluation timepoint. Overall response will be determined by the central imaging review based on the scheduled evaluations.

  After cycle 4 (each cycle is 28 days).

Secondary Outcomes (14)

• Progression free survival (PFS) (Cohort 1)

  At 2 and 5 years

• Overall survival (OS) (Cohort 1)

  At 2 and 5 years

• Duration of response (DOR) (Cohort 1)

  Up to 5 years

• Patients who have second surgeries (Cohort 1)

  Up to 5 years

• Patients who undergo gross-total resection after treatment (Cohort 1)

  Up to 5 years

Study Arms (1)

Entrectinib therapy, Cohort 1 and Cohort 2

EXPERIMENTAL

Cohort 1: Patients who are younger than 3 years of age diagnosed with NTRK1/2/3- or ROS1-fused high-grade glioma (HGG) will receive therapy as outline in Detailed Description. Cohort 2: Patients who are younger than 3 years of age diagnosed with NTRK1/2/3- or ROS1-fused CNS tumors other than HGG will receive therapy as outline in Detailed Description.

Drug: Entrectinib; Drug: Cyclophosphamide; Drug: Etoposide; Drug: Carboplatin; Biological: G-CSF; Biological: Pegfilgrastim; Procedure: Surgery

Interventions

Cyclophosphamide DRUG

Given intravenous (IV)

Also known as: Cytoxan®

Entrectinib therapy, Cohort 1 and Cohort 2

Etoposide DRUG

Given IV

Also known as: VP-16

Entrectinib therapy, Cohort 1 and Cohort 2

Carboplatin DRUG

Given IV

Also known as: Paraplatin®

Entrectinib therapy, Cohort 1 and Cohort 2

G-CSF BIOLOGICAL

Given subcutaneous (SQ) or IV

Also known as: Filgrastim

Entrectinib therapy, Cohort 1 and Cohort 2

Pegfilgrastim BIOLOGICAL

Given SQ as part of recommended Bridging Therapy instead of G-CSF.

Also known as: Neulasta

Entrectinib therapy, Cohort 1 and Cohort 2

Surgery PROCEDURE

A gross total resection or significant debulking may become possible if a response to entrectinib is seen.

Also known as: Surgical resection

Entrectinib therapy, Cohort 1 and Cohort 2

Entrectinib DRUG

Given orally (PO) or enterally

Also known as: Rozlytrek

Entrectinib therapy, Cohort 1 and Cohort 2

Eligibility Criteria

• Age: Up to 3 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age from birth to age \<3 years at the time of diagnosis (date of surgical resection/biopsy)
• Participant with presumed newly diagnosed tumor in the supratentorial compartment
• Patient must have measurable disease based on RAPNO criteria
• ≤84 days since surgery (resection or biopsy)
• Available tumor tissue for central review
• Parent/guardian has the ability to understand and the willingness to sign a written informed consent document according to institutional guidelines

You may not qualify if:

• Previous exposure to cytotoxic chemotherapy or radiotherapy
• Patients must be \<3 years of age at the time of diagnosis (date of surgical resection/biopsy)
• High-grade glioma (World Health Organization \[WHO\] grade III or IV) harboring NTRK1/2/3 or ROS1 gene fusions as determined by central pathology review
• Patients must have measurable disease as defined by RAPNO criteria
• Patients are eligible at the time of diagnosis, prior to any exposure to chemotherapy, targeted therapy, immunotherapy, cellular therapy or radiation
• ≤28 days since study screening
• Lansky score ≥50% and a minimum life expectancy of ≥ 12 weeks
• Neurologic deficits must have been stable for at least 7 days prior to study enrollment
• Hemoglobin ≥ 8 g/dL (without transfusion or erythropoietin use within 7 days prior to enrollment)
• Platelet count ≥ 75,000/µL (without transfusion within 7-day period prior to enrollment)
• Absolute neutrophil count \>1,000/µL
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5x the upper limit of normal (ULN)
• Bilirubin ≤ 1.5 x ULN
• Adequate renal function as defined by the following age-based serum creatinine concentrations:
• to \<1 year: 0.5 mg/dL

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead
• Hoffmann-La Roche: collaborator

Study Sites (4)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

RECRUITING

GRAACC Hospital (Grupo de Apoio ao Adolescente e à Criança com Câncer)

São Paulo, 04039-001, Brazil

RECRUITING

Hospital Santa Marcelina

São Paulo, 08270-070, Brazil

RECRUITING

King Hussein Cancer Center

Amman, 11941, Jordan

RECRUITING

Related Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

MeSH Terms

Conditions

Glioma; Central Nervous System Neoplasms

Interventions

entrectinib; Cyclophosphamide; Etoposide; Carboplatin; Granulocyte Colony-Stimulating Factor; Filgrastim; pegfilgrastim; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Nervous System Neoplasms; Neoplasms by Site; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Coordination Complexes; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Daniel Moreira, MD, MEd

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Daniel Moreira, MD, MEd

CONTACT

866-278-5833; referralinfo@stjude.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Pediatric patients \<3 years of age, with NTRK1/2/3 or ROS1-fused high-grade gliomas and other CNS tumors will be treated with frontline single-agent entrectinib.

Study Record Dates

• First Submitted: July 22, 2024
• First Posted: July 30, 2024
• Study Start: May 1, 2026
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2032
• Last Updated: April 22, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be made available at the time of article publication.
• Access Criteria: Data will be provided to researchers following a formal request with the following information: full name of requestor, affiliation, data set requested, and timing of when data is needed. As an informational point, the lead statistician and study principal investigator will be informed that primary results datasets have been requested.

Locations

JO (1); US (1); BR (2)