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A Pilot Study of Larotrectinib for Newly-Diagnosed High-Grade Glioma With NTRK Fusion
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.
Study details:
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.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
Exclusion criteria
Eligibility
Age eligible for study : 0 and older
Healthy volunteers accepted : No
Gender eligible for study: All
Things to know
Study dates
Study start: 2021-04-08
Primary completion: 2025-12-01
Study completion finish: 2025-12-01
Study type
TREATMENT
Phase
EARLY_PHASE1
Trial ID
NCT04655404
Intervention or treatment
DRUG: Larotrectinib
PROCEDURE: Larotrectinib surgical
Conditions
- • High Grade Glioma
- • Diffuse Intrinsic Pontine Glioma
Find a site
Closest Location:
Sydney Children's Hospital
Research sites nearby
Select from list below to view details:
Sydney Children's Hospital
Randwick, New South Wales, Australia
Queensland Children's Hospital
South Brisbane, Queensland, Australia
Perth Children's Hospital
Perth, Western Australia, Australia
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Participant Group/Arm | Intervention/Treatment |
---|---|
EXPERIMENTAL: Feasibility Cohort
| DRUG: Larotrectinib
|
EXPERIMENTAL: Surgical Cohort
| DRUG: Larotrectinib
|
What is the study measuring?
Primary outcome
Primary Outcome Measure | Primary Outcome Description | Primary Outcome Time Frame |
---|---|---|
Disease control rate | To assess the disease control rate (Complete Response \[CR\], Continued Complete Response \[CCR\], Partial Response \[PR\] and Stable Disease \[SD\]) of larotrectinib in young children newly diagnosed with HGG carrying NTRK fusion after 2 cycles of larotrectinib monotherapy. | At the end of Cycle 2 (each cycle is 28 days) |
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 | To assess the safety and tolerability of larotrectinib given in combination with chemotherapy or post-focal radiation therapy in young children newly diagnosed with HGG carrying NTRK fusion. This will be achieved by calculating the number of participants with, as well as frequency and severity of, larotrectinib-related Adverse Events as assessed by CTCAE v5.0. | From Day 1 of treatment through 30 days following end of protocol treatment |
Maximum Plasma Concentration [Cmax] of larotrectinib | To characterize the plasma pharmacokinetics (PK) of larotrectinib in children newly diagnosed with HGG carrying NTRK fusions who undergo a second definitive resection. This will be achieved by measuring the Maximum Plasma Concentration (Cmax) of larotrectinib in blood (plasma) samples collected at pre-dose (day -5), pre-surgery (day -1) and during surgery. | Days 1 through 5 of surgical cycle |
Tumor Concentration of larotrectinib | To characterize the tumor pharmacokinetics (PK) of larotrectinib in children newly diagnosed with HGG carrying NTRK fusions who undergo a second definitive resection by measuring the concentration of larotrectinib in tumor tissue collected on day 5 of surgical cycle | Day 5 of surgical surgical cycle |
Secondary outcome
Secondary Outcome Measure | Secondary Outcome Description | Secondary Outcome Time Frame |
---|---|---|
Objective response rate (ORR) | To assess the objective response rate (ORR) (Complete Response \[CR\] and Partial Response \[PR\]) of larotrectinib in children newly-diagnosed with HGG carrying NTRK fusion after 2 cycles of larotrectinib monotherapy. | At the end of Cycle 2 (each cycle is 28 days) |
Survival rate | To assess overall (OS) and progression-free survivals (PFS) of children newly diagnosed with HGG carrying NTRK fusion treated with a larotrectinib-containing regimen at 1, 3 and 5 years and compared to historical data from BABYPOG and HIT-SKK. | From date of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months |
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