This phase II trial studies the side effects and how well larotrectinib works in treating
patients with previously untreated TRK fusion solid tumors and TRK fusion acute leukemia that
has come back. Larotrectinib may stop the growth of cancer cells with TRK fusions by blocking
the TRK enzymes needed for cell growth.
I. To determine the objective response rate (ORR) of children with infantile fibrosarcoma
(IFS) treated with neoadjuvant larotrectinib prior to local control.
I. To determine event-free survival (EFS), overall survival (OS), and duration of response
(DoR) of children with IFS treated with neoadjuvant larotrectinib prior to local control.
II. To determine the ORR, EFS, OS, and DoR of children with newly diagnosed TRK fusion solid
tumors other than IFS treated with neoadjuvant larotrectinib prior to local control.
III. To describe the toxicity of larotrectinib in children with solid tumors and acute
IV. To determine the percentage of patients with TRK fusion solid tumors with detectable
circulating tumor deoxyribonucleic acid (DNA) at baseline and after 2 weeks, 4 weeks, 24
weeks of treatment, at the time of discontinuation of larotrectinib therapy, and at
I. To determine the EFS, OS, and DoR of children with TRK fusion solid tumors other than IFS
treated with adjuvant larotrectinib following upfront surgery with positive margins after
II. To determine the EFS, OS, and DoR of children with TRK fusion solid tumors who experience
a complete response to larotrectinib and subsequently discontinue larotrectinib therapy.
III. To determine the remission induction rate for patients with recurrent/refractory TRK
fusion leukemia when treated with larotrectinib.
IV. To evaluate the surgical morbidity and extent of resection of initially unresectable
tumors in patients with TRK fusion solid tumors who undergo surgical resection following
V. To evaluate mechanisms of response and resistance to larotrectinib in children with TRK
VI. To evaluate the morphologic features of TRK fusion solid tumors at time of initial biopsy
to further define criteria for pathologic diagnosis of these tumors.
VII. To evaluate immunohistochemistry for pan-TRK as a screening method for TRK fusion tumors
and in resection specimens following neoadjuvant treatment with larotrectinib.
VIII. To evaluate the histologic response to larotrectinib in resection specimens following
IX. To evaluate circulating tumor DNA for the detection of the emergence of resistance
mutations and recurrence in patients with TRK fusion solid tumors treated with larotrectinib.
X. To evaluate the ratio of cerebrospinal fluid (CSF) to concurrent plasma concentrations of
larotrectinib in patients with leukemia.
XI. To evaluate the change in neurocognitive/behavioral functioning over time between
baseline and 2 years post-diagnosis of patients treated on this protocol using
parent-reported adaptive functioning (Adaptive Behavior Assessment System [ABAS]-III General
Adaptive Composite), executive function (Behavior Rating Inventory of Executive Function
Scales-Preschool Version [BRIEF-P] or BRIEF-2 Global Executive Composite Score), psychosocial
functioning (Behavior Assessment System for Children [BASC]-3 Internalizing, Externalizing
and Behavioral Symptoms Indices) and quality of life (Pediatric Quality of Life Inventory
[PedsQL] Total score).
Patients receive larotrectinib orally (PO) or by nasogastric (NG) or gastric tube (G-tube)
twice daily (BID) on days 1-28. Treatment repeats every 28 days for up to 26 cycles in the
absence of disease progression or unacceptable toxicity. Patients whose tumors shrink
sufficiently while taking larotrectinib may undergo surgical resection of their tumor while
After completion of study treatment, patients are followed up at 3, 6, 12, 18, 24, 30, 36,
and 48 months and annually thereafter for up to 5 years from the date of study entry.
Central Nervous System Neoplasm, Infantile Fibrosarcoma, Recurrent Acute Leukemia, Refractory Acute Leukemia, Solid Neoplasm
If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.
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