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)

St. Jude Children's Research Hospital6 个研究点分布在 4 个国家目标入组 52 人开始时间: 2026年5月1日最近更新: 2026年5月13日

适应症

干预措施

试验速览

阶段: 2 期
状态: 招募中
发起方: St. Jude Children's Research Hospital
入组人数: 52
试验地点: 6
主要终点: Overall response rate (ORR) (Cohort 1)

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

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.

详细描述

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.

研究设计

研究类型: Interventional
分配方式: Na
干预模型: Single Group
主要目的: Treatment
盲法: None

入排标准

年龄范围: — 至 3 Years（Child）
性别: All
接受健康志愿者: 否

入选标准

•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

排除标准

•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
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