Entrectinib as a Single Agent in Upfront Therapy for Children <3 Years of Age With NTRK1/2/3 or ROS1-FUSED CNS Tumors
NCT Number: NCT06528691
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: High Grade Glioma|CNS Tumor
Interventions: DRUG: Entrectinib|DRUG: Cyclophosphamide|DRUG: Etoposide|DRUG: Carboplatin|BIOLOGICAL: G-CSF|BIOLOGICAL: Pegfilgrastim|PROCEDURE: Surgery
Sponsor: St. Jude Children's Research Hospital
Collaborators: Hoffmann-La Roche
Sex: ALL
Age: CHILD
Enrollment: 52
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-10
Completion Date: 2032-11
Locations: St. Jude Children's Research Hospital, Memphis, Tennessee, 38105, United States

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.

Primary Outcome Measures: 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., After cycle 4 (each cycle is 28 days).
Secondary Outcome Measures: 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., At 2 and 5 years|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., At 2 and 5 years|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., Up to 5 years|Patients who have second surgeries (Cohort 1), Percentage of patients who had second surgeries., Up to 5 years|Patients who undergo gross-total resection after treatment (Cohort 1), Percentage of patients who underwent a gross-total resection., Up to 5 years|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., After cycle 4 (each cycle is 28 days).|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., At 2 and 5 years|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., At 2 and 5 years|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., Up to 5 years|Patients who have second surgeries (Cohort 2), Percentage of patients who had second surgeries. \[Time Frame: Up to 5 years\], Up to 5 years|Patients who undergo gross-total resection after treatment (Cohort 2), Percentage of patients who underwent a gross-total resection., Up to 5 years|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., Up to 5 years|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., Up to 5 years|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., Up to 5 years