A Pilot Study of Larotrectinib for Newly-Diagnosed High-Grade Glioma With NTRK Fusion
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|ClinicalTrials.gov Identifier: NCT04655404|
Recruitment Status : Recruiting
First Posted : December 7, 2020
Last Update Posted : August 12, 2022
This is a pilot study that will evaluate disease status in children that have been newly diagnosed high-grade glioma with TRK fusion. The evaluation will occur after 2 cycles of the medication (Larotrectinib) have been given.
The study will also evaluate the safety of larotrectinib when given with chemotherapy in your children; as well as the safety larotrectinib when given post-focal radiation therapy.
|Condition or disease||Intervention/treatment||Phase|
|High Grade Glioma Diffuse Intrinsic Pontine Glioma||Drug: Larotrectinib Procedure: Larotrectinib surgical||Early Phase 1|
In this pilot study, we will assess the disease control rate (Continued Complete Response-CCR, Complete Response-CR, Partial Response-PR and Stable Disease-SD) as well as survival rate (overall survival- OS and progression free survival- PFS) in children with newly diagnosed HGG with TRK fusion who receive 2 cycles of larotrectinib monotherapy administered orally, twice daily, at 100 mg/m2 continuously on a 28-day cycle schedule. After 2 monotherapy cycles of larotrectinib, patients with CCR or CR will continue to receive larotrectinib maintenance therapy as monotherapy for a total of 12 cycles. Continuation of treatment beyond 12 cycles, and up to 24 cycles, may be considered for patients on Larotrectinib monotherapy if they are receiving clinical benefit from the study, at the discretion of the treating physician.
Patients ≤ 48 months with PR or SD after 2 cycles of larotrectinib will go on to receive combination therapy with standard backbone chemotherapy (BABYPOG or HIT-SKK). Patients > 48 months of age (or patients ≥ 36 months of age, or patients with DIPG >18 months of age, at the discretion of the local investigator) will receive focal radiation therapy. A surgical cohort study will be explored whereby patients who have had a tumor biopsy/partial resection at their local institution and are planned to subsequently undergo definitive resection will receive 3-5 days (6-10 doses) of larotrectinib pre-surgery.
The study design of this trial requires 15 patients evaluable for disease control and for safety/ toxicity of larotrectinib as monotherapy. The surgical cohort will enroll up to 4 patients and will count towards the total 15 evaluable patients. A minimum of 6 patients will be evaluable for safety toxicity of larotrectinib in combination with standard-of-care chemotherapy or radiotherapy.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||15 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Pilot and Surgical Study of Larotrectinib for Treatment of Children With Newly-Diagnosed High-Grade Glioma With NTRK Fusion|
|Actual Study Start Date :||April 8, 2021|
|Estimated Primary Completion Date :||December 1, 2025|
|Estimated Study Completion Date :||December 1, 2025|
Larotrectinib will be administered orally, twice daily, at 100 mg/m2 continuously on a 28-day cycle schedule.
Larotrectinib monotherapy x2 cycles followed by disease evaluation
Other Name: Larotrectinib with or without chemotherapy backbone
Procedure: Larotrectinib surgical
Surgical cohort: Larotrectinib x 3-5 days prior to definitive surgery
- Disease control rate [ Time Frame: 24 months ]To assess the disease control rate of larotrectinib in young children with newly-diagnosed high-grade glioma with NTRK fusion after 2 cycles of larotrectinib monotherapy
- Incidence of Treatment- Emergent Adverse Events (Safety) of larotrectinib [ Time Frame: 24 months ]To assess the safety of larotrectinib when given in combination with chemotherapy or post-focal radiation therapy, assessed by CTCAE v5.0
- Measurement of Are Under the Curve (AUC) of larotrectinib [ Time Frame: 24 months ]To characterize the area under the plasma concentration versus time curve (AUC) of larotrectinib in surgical patients through the measurement of blood pharmacokinetics
- Dose-response relationship of larotrectinib [ Time Frame: 24 months ]To characterize the dose-response relationship of larotrectinib in surgical patients through the measurement of blood pharmacodynamics
- Response rate [ Time Frame: 24 months ]To assess the objective response rate (ORR) (Complete Response [CR] and Partial Response [PR]) of larotrectinib in children with newly-diagnosed high-grade glioma with NTRK fusion after 2 cycles of larotrectinib monotherapy.
- Survival rate [ Time Frame: 60 months ]To assess overall (OS) and progression-free survivals (PFS) of children with high-grade gliomas treated with a larotrectinib-containing regimen at 1, 3 and 5 years defined as date of death or earliest date of failure.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04655404
|Contact: Dorothy Crabtree||614-722-8693||Dorothy.Crabtree@nationwidechildrens.org|
|Study Chair:||Susan Chi, MD||Dana Farber/ Boston Children's Cancer and Blood Disorders Center|
|Study Chair:||Maryam Fouladi||Nationwide Children's Hospital|