NCT02285439

Study of MEK162 for Children With Low-Grade Gliomas

Phase I-II Study of MEK 162 for Children With Low-Grade Gliomas and Other Ras/Raf/ERK Pathway Activated Tumors

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 105 (actual)
• Sponsor: Children's Hospital Los Angeles · Academic / Other
• Sex: All
• Age: 1 Year – 18 Years
• Healthy volunteers: Not accepted

Summary

The goal of this clinical trial is to study the drug MEK162 in children with a brain tumor call low-grade glioma, as well as in children with other tumors in which a specific growth signal is abnormally turned on. The main questions it aims to answer are: What is the correct dose of MEK162 in children? What are the side effects of MEK162 in children? Is MEK162 effective in children with low-grade glioma? Participants on the study receive MEK162 by mouth twice daily for up to 2 years.

Detailed description

PROTOCOL SUMMARY: Phase 1: Patients with non-hematologic malignancies that are recurrent, progressive, or refractory after standard up-front therapy receiving MEK162 will define the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), and toxicity profile. Phase 2: Patients with recurrent or progressive tumors signaling through the ras/raf pathway after standard up-front therapy will be treated in three strata to define the activity of MEK162. Stratum 1: Pediatric patients with recurrent or progressive low-grade glioma (LGG) characterized by a BRAF truncated fusion (KIAA1549 and similar translocations). Stratum 2: Pediatric patients with neurofibromatosis type 1 (NF1) and recurrent or progressive LGG. Stratum 3: Pediatric patients with recurrent or progressive tumors thought to involve the ras/raf/MAP pathway but not included in strata 1 or 2. This includes any LGG not included in strata 1 or 2 (i.e., any LGG without a BRAF truncated fusion in a patient without NF1), any tumor other than LGG in a patient with NF1, and any other tumor with a known activating BRAF, NRAS or KRAS mutation. Target validation phase: Patient enrolled on the phase 2 component (any stratum) for whom tumor biopsy or resection is clinically indicated. Patients will receive MEK162 for 7 to 21 days prior to their surgery. Samples will be analyzed for concentration of drug and target inhibition. Length of therapy: Protocol treatment will last approximately 48 weeks from the start of MEK162 in the absence of significant toxicity. Treatment will be administered based on the dose escalation schema for phase 1. Patients in the phase 2 component of the trial will also receive a planned 48 weeks of therapy. Those undergoing planned tumor resection based on clinical criteria will be eligible to receive 7-21 days of treatment with MEK162 prior to the surgical procedure. Imaging to assess response will be obtained at the end of cycle 1 (+/- 1 week), at the end of cycle 3 (+/- 2 weeks) and after every three cycles thereafter (+/- 2 weeks). A cycle will consist of 28 days (+/- 3 days) and MEK162 will be given continuously. Patients deriving benefit may continue therapy beyond study completion but all protocol specific evaluations (other than survival or progression) will conclude after one year. All patients will be followed with progression as the end point.

Conditions

• Low-Grade Gliomas
• Malignant Neoplasms, Brain
• Soft Tissue Neoplasms

Interventions

Type	Name	Description
DRUG	MEK162	• MEK162 is currently supplied as film-coated tablets in dose strength of 15 mg. The film-coated tablets consist of MEK162 drug substance, lactose monohydrate, microcrystalline cellulose, colloidal silicon dioxide, croscarmellose sodium, magnesium stearate, and a commercial film coating. The original tablets are yellow to dark yellow capsule-shaped

Timeline

• Start date: 2016-05-04
• Primary completion: 2022-11-02
• Completion: 2025-08-01
• First posted: 2014-11-07
• Last updated: 2025-10-07
• Results posted: 2025-10-07

Locations

15 sites across 1 country: United States

Regulatory

• FDA-regulated drug study