New hope for toddlers with rare brain tumors: targeted drug entrectinib tested

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

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