Last updated 5 days ago
Entrectinib as a Single Agent in Upfront Therapy for Children <3 Years of Age With NTRK1/2/3 or ROS1-FUSED CNS Tumors
52 patients around the world
Available in United States, Brazil
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.
St. Jude Children's Research Hospital
2Research sites
52Patients around the world
This study is for people with
Brain Tumor
Glioma
Central nervous system neoplasm
Central nervous system tumor
Requirements for the patient
To 3 Years
All Gender
Medical requirements
- 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.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.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.
- Screening Phase.Previous exposure to cytotoxic chemotherapy or radiotherapy.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.
Sites
Grupo de Apoio Ao Adolescente E A Crianca Com Cancer - GRAACC
Recruiting
Hospital Santa Marcelina
Recruiting
StudyGLOBOTRK
SponsorSt. Jude Children's Research Hospital
Study typeInterventional
Conditions
GliomaCentral nervous system tumor
Requirements
To 3 YearsAll Gender
Unique study IDclinicaltrials.gov
NCT06528691
