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

Launched by ST. JUDE CHILDREN'S RESEARCH HOSPITAL · Jul 25, 2024

Keywords

ClinConnect Summary

This clinical trial is studying a medication called entrectinib to see how well it works for children under 3 years old who have certain types of brain tumors known as high-grade gliomas or other central nervous system (CNS) tumors. These tumors must have specific gene changes, known as fusions, involving NTRK or ROS1. The goal is to find out if entrectinib can help treat these young patients right after their diagnosis, before they receive any other cancer treatments.

To be eligible for this trial, children must be less than 3 years old at the time of their diagnosis and have measurable tumors that fit the study criteria. They should have been diagnosed no more than 42 days before joining the trial and must have stable health conditions, meaning their symptoms should not have worsened recently. Families participating can expect to be closely monitored during the trial, with regular visits for treatment and check-ups. It’s essential for parents or guardians to understand the study and provide consent before their child can participate. This trial aims to explore new treatment options for very young patients facing serious health challenges.

Gender

ALL

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