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High Grade GliomaPhase 2NCT06528691

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

A Phase 2 study testing Entrectinib, Cyclophosphamide and Etoposide in people with High Grade Glioma and CNS Tumor, run by St. Jude Children's Research Hospital at 6 sites in 4 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages Up to 3 years
Conditions the study is for
High Grade Glioma, CNS Tumor
What is being tested?
Entrectinib, Cyclophosphamide and Etoposide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
52 participants
Where
6 sitesin 4 countries
Study dates
1 May 2026to Nov 2032
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 3 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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
Show all 44Show fewer
  • 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

Who cannot join

  • 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
Show all 11Show fewer
  • 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

Trial locations and contacts

6 sites in 4 countries. Contact the study team or a site near you to ask about taking part.

Tabatha E. Doyle, RN contact

901-595-2544

tabatha.doyle@stjude.org

Daniel Moreira, MD, MEd contact

901-585-1911

daniel.moreira@stjude.org

6 sites in 4 countries

Brazil3 sites, 3 recruiting

  • Hospital de Câncer de Barretos

    Barretos, São Paulo, 14784400

    Thais J. Vampre, MD, 17 3321-6647, thaisjunq79@gmail.com

    Thais J. Vampre, MD

    Recruiting

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

    São Paulo, 04039-001

    Andrea M. Cappellano, MD, +55 11 5080-8400, andreacappellano@graacc.org.br

    Andrea M. Cappellano, MD

    Recruiting

  • Hospital Santa Marcelina

    São Paulo, 08270-070

    Sidnei Epelman, MD, +55 11 2522-2472, epelman@inctrbrasil.org

    Sidnei Epelman, MD

    Recruiting

Other trials in Brazil

United States1 site, 1 recruiting

  • St. Jude Children's Research Hospital

    Memphis, Tennessee, 38105

    Tabatha E. Doyle, RN, 901-595-2544, tabatha.doyle@stjude.org

    GLOBOTRK@stjude.com

    Recruiting

Other trials in United States

Jordan1 site, 1 recruiting

  • King Hussein Cancer Center

    Amman, 11941

    Nisreen Amayiri, MD, (962 6) 5300460 ext. 6376, namayiri@khcc.jo

    Nisreen Amayiri, MD

    Recruiting

Other trials in Jordan

Peru1 site, 1 recruiting

  • Instituto Nacional de Enfermedades Neoplásicas

    Lima

    Rosdali Coronado, MD, +51 991765893, rosdali.diaz.c@upch.pe

    Rosdali Coronado, MD

    Recruiting

Other trials in Peru

About this study

Official title: PHASE 2 Study of Entrectinib as a Single Agent in Upfront Therapy for Children <3 Years of Age With NTRK1/2/3 or ROS1-FUSED CNS Tumors (GLOBOTRK)

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.

Read the 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.

Being tested
Entrectinib, Cyclophosphamide, Etoposide, Carboplatin, G-CSF
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
Medical subject headings
Glioma, Central Nervous System Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EntrectinibDrug

    Also called Rozlytrek

    Given orally (PO) or enterally

  • CyclophosphamideDrug

    Also called Cytoxan®

    Given intravenous (IV)

  • EtoposideDrug

    Also called VP-16

    Given IV

  • CarboplatinDrug

    Also called Paraplatin®

    Given IV

  • G-CSFBiological

    Also called Filgrastim

    Given subcutaneous (SQ) or IV

  • PegfilgrastimBiological

    Also called Neulasta

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

  • SurgeryProcedure or surgery

    Also called Surgical resection

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

Study groups in NCT06528691
Study groupRoleWhat they receive
Entrectinib therapy, Cohort 1 and Cohort 2ExperimentalCohort 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.
Receives: Drug: Entrectinib; Drug: Cyclophosphamide; Drug: Etoposide; Drug: Carboplatin; Biological: G-CSF; Biological: Pegfilgrastim; Procedure: Surgery

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: After cycle 4 (each cycle is 28 days).

Secondary outcomes (14)

  1. Progression free survival (PFS) (Cohort 1)

    PFS is defined as the time from initiation of protocol treatment to first event (progressive disease, death due to any cause), or date last follow-up among those who have not had an event. Described using Kaplan Meier method.

    Measured: At 2 and 5 years

  2. Overall survival (OS) (Cohort 1)

    OS is defined as the time from date of diagnosis to date of death due to any cause or date last follow-up. Described using Kaplan Meier method.

    Measured: At 2 and 5 years

  3. Duration of response (DOR) (Cohort 1)

    DOR is defined as time from date of first response (partial or complete) until the date of progression or last follow-up. Described as median time.

    Measured: Up to 5 years

  4. Patients who have second surgeries (Cohort 1)

    Percentage of patients who had second surgeries.

    Measured: Up to 5 years

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

    Percentage of patients who underwent a gross-total resection.

    Measured: Up to 5 years

  6. ORR (Cohort 2)

    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.

    Measured: After cycle 4 (each cycle is 28 days).

  7. PFS (Cohort 2)

    PFS is defined as the time from initiation of protocol treatment to first event (progressive disease, death due to any cause), or date last follow-up among those who have not had an event. Described using Kaplan Meier method.

    Measured: At 2 and 5 years

  8. OS (Cohort 2)

    OS is defined as the time from date of diagnosis to date of death due to any cause or date last follow-up. Described using Kaplan Meier method.

    Measured: At 2 and 5 years

  9. DOR (Cohort 2)

    DOR is defined as time from date of first response (partial or complete) until the date of progression or last follow-up. Described as median time.

    Measured: Up to 5 years

  10. Patients who have second surgeries (Cohort 2)

    Percentage of patients who had second surgeries. [Time Frame: Up to 5 years]

    Measured: Up to 5 years

  11. Patients who undergo gross-total resection after treatment (Cohort 2)

    Percentage of patients who underwent a gross-total resection.

    Measured: Up to 5 years

  12. Incidence of adverse events (Cohort 1 and 2)

    Percentage of adverse events on therapy including Entrectinib, captured using National Cancer Institute Common Terminology Criteria for Adverse Events 5.0.

    Measured: Up to 5 years

  13. Number of patients screened versus enrolled and treated (Cohort 1 and 2)

    Number of enrolled and treated patients as a percentage of number of patients screened and eligible for study.

    Measured: Up to 5 years

  14. Time from initial diagnostic surgery to screening and enrollment (Cohort 1 and 2)

    Median time in days from initial surgery to screening and enrollment on study.

    Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Jul 2024
  2. Study start1 May 2026
  3. Primary completionNov 2027 (estimated)
  4. Study completionNov 2032 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
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.
Masking
None (open label)
Enrolment
52 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06528691
Sponsor's protocol ID
GLOBOTRK
Other IDs
NCI-2024-02977
Status last verified
Nov 2026
First submitted
22 Jul 2024
Last updated
3 Nov 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Individual participant de-identified datasets containing the variables analyzed in the published article will be made available (related to the study primary or secondary objectives contained in the publication). Supporting documents such as the protocol, statistical analyses plan, and informed consent are available through the CTG website for the specific study. Data used to generate the published article will be made available at the time of article publication. Investigators who seek access to individual level de-identified data will contact the computing team in the Department of Biostatistics (ClinTrialDataRequest@stjude.org) who will respond to the data request.

Publications

  • Bagchi A, Chiang J, Pinto S, Dhanda S, Gajjar A. Infant-Type Hemispheric Gliomas: A Review of Clinical, Radiologic, Histopathologic, and Molecular Features. J Natl Compr Canc Netw. 2025 Nov;23(11):e257064. doi: 10.6004/jnccn.2025.7064.

    PubMed 41213248

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Entrectinib, Cyclophosphamide and Etoposide in people with High Grade Glioma and CNS Tumor, run by St. Jude Children's Research Hospital at 6 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 44 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 3 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in Brazil, United States, Jordan, Peru. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Tabatha E. Doyle, RN (901-595-2544, tabatha.doyle@stjude.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall response rate (ORR) (Cohort 1) (time frame: After cycle 4 (each cycle is 28 days).). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06528691, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Nov 2026.

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