NCT06528691

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

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 52 (estimated)
• Sponsor: St. Jude Children's Research Hospital · Academic / Other
• Sex: All
• Age: 3 Years
• Healthy volunteers: Not accepted

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

Interventions

Type	Name	Description
DRUG	Entrectinib	Given orally (PO) or enterally
DRUG	Cyclophosphamide	Given intravenous (IV)
DRUG	Etoposide	Given IV
DRUG	Carboplatin	Given IV
BIOLOGICAL	G-CSF	Given subcutaneous (SQ) or IV
BIOLOGICAL	Pegfilgrastim	Given SQ as part of recommended Bridging Therapy instead of G-CSF.
PROCEDURE	Surgery	A gross total resection or significant debulking may become possible if a response to entrectinib is seen.

Timeline

• Start date: 2026-04-01
• Primary completion: 2027-11-01
• Completion: 2032-11-01
• First posted: 2024-07-30
• Last updated: 2026-03-23

Locations

2 sites across 2 countries: United States, Jordan

Regulatory

• FDA-regulated drug study