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

NCT ID: NCT06528691

Last Updated: 2026-01-12

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-02-28
• Study Completion Date: 2032-11-30

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.

Detailed Description

PRIMARY OBJECTIVE

• To determine the overall response rate of entrectinib when used as first line therapy in patients who are younger than 3 years of age with NTRK1/2/3- or ROS1-fused high-grade glioma (HGG) (Cohort 1).

SECONDARY OBJECTIVES

• To estimate the 2-year and 5-year progression free survival (PFS) and overall survival (OS) in patients who are younger than 3 years of age with NTRK1/2/3- or ROS1-fused HGG treated with entrectinib as first line therapy (Cohort 1).
• To estimate the duration of response (DOR) in patients who are younger than 3 years of age with NTRK1/2/3- or ROS1-fused HGG treated with entrectinib as first line therapy (Cohort 1).
• To evaluate the fraction of patients with NTRK1/2/3- or ROS1-fused HGG treated who have second surgeries and a gross-total resection after treatment with entrectinib is achieved, overall and by country and hospital (Cohort 1).
• To describe the overall response rate of entrectinib when used as first line therapy in patients who are younger than 3 years of age with NTRK1/2/3- or ROS1-fused CNS tumors other than HGG (Cohort 2).
• To estimate the 2-year and 5-year PFS and OS in patients who are younger than 3 years of age with NTRK1/2/3- or ROS1-fused CNS tumors other than HGG treated with entrectinib as first line therapy (Cohort 2).
• To estimate the duration of response (DOR) in patients who are younger than 3 years of age with NTRK1/2/3- or ROS1-fused CNS tumors other than HGG treated with entrectinib as first line therapy (Cohort 2).
• To evaluate the fraction of patients with NTRK1/2/3- or ROS1-fused CNS tumors other than HGG who have second surgeries and a gross-total resection after treatment with entrectinib is achieved, overall and by country and hospital (Cohort 2).
• To describe toxicities experienced by patients younger than 3 years of age treated with entrectinib (Cohort 1 and 2).
• To evaluate number of patients that are screened for the study and eligible versus enrolled and treated with entrectinib (Cohort 1 and 2).
• To measure the time intervals (days) from time of initial diagnostic surgery to screening and enrollment in this study (Cohort 1 and 2).

The trial will have 2 cohorts: Cohort 1: patients diagnosed with NTRK1/2/3- or ROS1-fused high-grade glioma (HGG) and Cohort 2: patients diagnosed with NTRK1/2/3- or ROS1-fused CNS tumors other than HGG.

Patients receive entrectinib enterally once daily (QD) 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. Patients requiring bridging therapy prior to starting entrectinib may receive cyclophosphamide intravenously (IV) over 1 hour on day 1, etoposide IV over 1 hour on day 1 and 2, carboplatin IV over 1 hour on day 2, filgrastim subcutaneously (SC) or IV or pegfilgrastim SC on day 3.

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.

After treatment, patients will be followed for 5 years.

Conditions

High Grade Glioma; CNS Tumor

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Entrectinib therapy, Cohort 1 and Cohort 2

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.

Group Type: EXPERIMENTAL

Entrectinib

Intervention Type: DRUG

Given orally (PO) or enterally

Cyclophosphamide

Intervention Type: DRUG

Given intravenous (IV)

Etoposide

Intervention Type: DRUG

Given IV

Carboplatin

Intervention Type: DRUG

Given IV

G-CSF

Intervention Type: BIOLOGICAL

Given subcutaneous (SQ) or IV

Pegfilgrastim

Intervention Type: BIOLOGICAL

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

Surgery

Intervention Type: PROCEDURE

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

Interventions

Entrectinib

Given orally (PO) or enterally

Intervention Type: DRUG

Cyclophosphamide

Given intravenous (IV)

Intervention Type: DRUG

Etoposide

Given IV

Intervention Type: DRUG

Carboplatin

Given IV

Intervention Type: DRUG

G-CSF

Given subcutaneous (SQ) or IV

Intervention Type: BIOLOGICAL

Pegfilgrastim

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

Intervention Type: BIOLOGICAL

Surgery

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

Intervention Type: PROCEDURE

Other Intervention Names

Rozlytrek; Cytoxan®; VP-16; Paraplatin®; Filgrastim; Neulasta; Surgical resection

Eligibility Criteria

Inclusion Criteria

• 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

• 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:

• 0 to <1 year: 0.5 mg/dL
• 1 to <2 years: 0.6 mg/dL
• 2 to 3 years: 0.8 mg/dL
• Adequate cardiac function as defined by electrocardiogram (ECG) with Fridericia's corrected QT interval (QTc) ≤ 450 msec and echocardiogram left ventricular ejection fraction (LVEF) >50%
• Screening and enrollment consents signed
• Willingness and ability to comply with treatment plan, scheduled visits, laboratory tests and other study procedures

• Patients must be <3 years of age at the time of diagnosis (date of surgical resection/biopsy)
• CNS tumor other than HGG 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.
• ALT and 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:

• 0 to <1 year: 0.5 mg/dL
• 1 to <2 years: 0.6 mg/dL
• 2 to 3 years: 0.8 mg/dL
• Adequate cardiac function as defined by ECG with QTc ≤ 450 msec and echocardiogram LVEF >50%
• Screening and enrollment consents signed
• Willingness and ability to comply with treatment plan, scheduled visits, laboratory tests and other study procedures

Exclusion Criteria

• Previous exposure to cytotoxic chemotherapy or radiotherapy

• Clinically significant medical disorder that could compromise the ability to tolerate study therapy or would interfere with the study procedures or results history
• History of recent (3 months) symptomatic congestive heart failure
• Known active, uncontrolled infection (bacterial, fungal, or viral)
• Receiving enzyme inducing antiepileptic drugs (EIAEDs)
• Any prior cancer therapy including chemotherapy (excluding Bridging Chemotherapy Cycle), targeted therapy, immunotherapy, cellular therapy, or radiation
• Receiving another investigational agent concurrently
• Surgery within 2 weeks prior to treatment enrollment
• Patients with known hypersensitivity to excipients of the investigational medicinal product
• Active gastrointestinal disease or malabsorption disorder (e.g. Crohn's disease, ulcerative colitis, short-gut syndrome) that would impair drug absorption
• Inability to take medication enterally

• Maximum Eligible Age: 3 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: collaborator

St. Jude Children's Research Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Daniel Moreira, MD, MEd

Role: PRINCIPAL_INVESTIGATOR

St. Jude Children's Research Hospital

Locations

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Daniel Moreira, MD, MEd

Role: CONTACT

referralinfo@stjude.org

866-278-5833

Facility Contacts

Daniel Moreira, MD, MEd

Role: primary

referralinfo@stjude.org

866-278-5833

Related Links

http://www.stjude.org

St. Jude Children's Research Hospital

http://www.stjude.org/protocols

Clinical Trials Open at St. Jude

Other Identifiers

NCI-2024-02977

Identifier Type: REGISTRY

Identifier Source: secondary_id

GLOBOTRK

Identifier Type: -

Identifier Source: org_study_id