Trial Title:
Entrectinib as a Single Agent in Upfront Therapy for Children <3 Years of Age With NTRK1/2/3 or ROS1-FUSED CNS Tumors
NCT ID:
NCT06528691
Condition:
High Grade Glioma
CNS Tumor
Conditions: Official terms:
Glioma
Central Nervous System Neoplasms
Cyclophosphamide
Carboplatin
Etoposide
Entrectinib
Conditions: Keywords:
CNS Tumors
High Grade Glioma with NTRK1/2/3 gene fusion
High Grade Glioma with ROS1 gene fusion
CNS tumor other than HGG harboring NTRK1/2/3 gene fusion
CNS tumor other than HGG harboring ROS1 gene fusion
Children
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
Pediatric patients <3 years of age, with NTRK1/2/3 or ROS1-fused high-grade gliomas and
other CNS tumors will be treated with frontline single-agent entrectinib.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Entrectinib
Description:
Given orally (PO) or enterally
Arm group label:
Entrectinib therapy, Cohort 1 and Cohort 2
Other name:
Rozlytrek
Intervention type:
Drug
Intervention name:
Cyclophosphamide
Description:
Given intravenous (IV)
Arm group label:
Entrectinib therapy, Cohort 1 and Cohort 2
Other name:
Cytoxan®
Intervention type:
Drug
Intervention name:
Etoposide
Description:
Given IV
Arm group label:
Entrectinib therapy, Cohort 1 and Cohort 2
Other name:
VP-16
Intervention type:
Drug
Intervention name:
Carboplatin
Description:
Given IV
Arm group label:
Entrectinib therapy, Cohort 1 and Cohort 2
Other name:
Paraplatin®
Intervention type:
Biological
Intervention name:
G-CSF
Description:
Given subcutaneous (SQ) or IV
Arm group label:
Entrectinib therapy, Cohort 1 and Cohort 2
Other name:
Filgrastim
Intervention type:
Biological
Intervention name:
Pegfilgrastim
Description:
Given SQ as part of recommended Bridging Therapy instead of G-CSF.
Arm group label:
Entrectinib therapy, Cohort 1 and Cohort 2
Other name:
Neulasta
Intervention type:
Procedure
Intervention name:
Surgery
Description:
A gross total resection or significant debulking may become possible if a response to
entrectinib is seen.
Arm group label:
Entrectinib therapy, Cohort 1 and Cohort 2
Other name:
Surgical resection
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.
Criteria for 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
- ≤42 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
Gender:
All
Minimum age:
N/A
Maximum age:
3 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
St. Jude Children's Research Hospital
Address:
City:
Memphis
Zip:
38105
Country:
United States
Status:
Recruiting
Contact:
Last name:
Daniel Moreira, MD, MEd
Phone:
866-278-5833
Email:
referralinfo@stjude.org
Investigator:
Last name:
Daniel Moreira, MD, MEd
Email:
Principal Investigator
Start date:
December 2024
Completion date:
November 2032
Lead sponsor:
Agency:
St. Jude Children's Research Hospital
Agency class:
Other
Collaborator:
Agency:
Hoffmann-La Roche
Agency class:
Industry
Source:
St. Jude Children's Research Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06528691
http://www.stjude.org
http://www.stjude.org/protocols
