Larotrectinib (CONNECT1903)

This is a Phase I 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 children; as well as the safety larotrectinib when given post-focal radiation therapy.

Larotrectinib specifically inhibits tropomyosin receptor kinases (TRK), a group of signaling proteins that play an important role in cellular communication and tumor growth. The study therefore treats tumors whose genetic information has changed in this area (NTRK fusion).

Participants receive 2 cycles of larotrectinib monotherapy administered orally, twice daily either as capsules or as suspension at 100 mg/m2 continuously on a 28-day cycle schedule. After 2 monotherapy cycles of larotrectinib, participants with CCR (Continued Complete Response) or CR (Complete Response) 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 (Partial Response) or SD (Stable Disease) 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.