Entrectinib treatment for young children with specific CNS tumors

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 study is testing if a new treatment called entrectinib can help young children under 3 with certain brain tumors feel better and live longer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 52 (estimated)
• Ages: N/A to 3 Years
• Sex: All
• Sponsor: St. Jude Children's Research Hospital (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation, entrectinib, cyclophosphamide
• Locations: 6 sites (Memphis, Tennessee and 5 other locations)
• Trial ID: NCT06528691 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness of entrectinib as a first-line treatment for children under 3 years old diagnosed with high-grade gliomas or other central nervous system tumors that have NTRK1/2/3 or ROS1 gene fusions. The study aims to determine the overall response rate, progression-free survival, and overall survival rates in these young patients. Additionally, it will assess the duration of response and the rate of gross-total resection achieved after treatment. The trial includes two cohorts: one for high-grade gliomas and another for CNS tumors other than high-grade gliomas.

Who should consider this trial

Good fit: Ideal candidates are children under 3 years of age with newly diagnosed high-grade gliomas or CNS tumors harboring specific gene fusions.

Not a fit: Patients who have previously received cytotoxic chemotherapy or radiotherapy will not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve outcomes for very young patients with aggressive CNS tumors.

How similar studies have performed: While this approach is novel for this specific age group and tumor types, similar studies have shown promise with targeted therapies in pediatric oncology.

Eligibility criteria

Inclusion Criteria: Screening Phase

* 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

Exclusion Criteria: Screening Phase

* Previous exposure to cytotoxic chemotherapy or radiotherapy

Inclusion Criteria: COHORT 1

* 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

Inclusion Criteria: COHORT 2

* 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: COHORT 1 AND 2

* 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

Where this trial is running

Memphis, Tennessee and 5 other locations

• St. Jude Children's Research Hospital — Memphis, Tennessee, United States (Recruiting)
• Hospital de Câncer de Barretos — Barretos, São Paulo, Brazil (Recruiting)
• GRAACC Hospital (Grupo de Apoio ao Adolescente e à Criança com Câncer) — São Paulo, Brazil (Recruiting)
• Hospital Santa Marcelina — São Paulo, Brazil (Recruiting)
• King Hussein Cancer Center — Amman, Jordan (Recruiting)
• Instituto Nacional de Enfermedades Neoplásicas — Lima, Peru (Recruiting)

Study contacts

• Principal investigator: Daniel Moreira, MD, MEd — St. Jude Children's Research Hospital
• Study coordinator: Tabatha E. Doyle, RN

Conditions High Grade Glioma; CNS Tumor; 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