Study of MEK162 for Children With Low-Grade Gliomas

NCT02285439 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: CHLA-15-00146
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 15

Brief 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.

Conditions

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

Keywords

Pediatric Oncology; Ras/Raf pathway; Low-Grade Glioma; MEK inhibitor

Outcome Measures

Primary Outcomes (2)

• Best Overall Response Rate (Strata 1 and 2)

  For each stratum, the percentage of patients achieving at least a minor response (defined as greater than or equal to 25% decrease in maximal two dimensional measurements compared to baseline) during the first 12 cycles (nominally 48 weeks) of treatment will be reported.

  48 weeks

• 12 Cycle Progression-free and Overall Survival (Strata 1 and 2)

  Progression free and overall survival will be reported as Kaplan-Meier estimate who are alive without disease progression, alive with disease progression, deceased without disease progression, and deceased with disease progression 12 cycles (48 weeks) after treatment initiation.

  48 weeks

Study Arms (3)

Phase 1

EXPERIMENTAL

Patients with non-hematologic malignancies that are recurrent, progressive, or refractory after standard up-front therapy receiving MEK162 will define the MTD, DLT, and toxicity profile.

Drug: MEK162

Phase 2

EXPERIMENTAL

Children with recurrent tumors signaling through the Ras/Raf pathway will be treated in 3 strata to define the activity of MEK162. S1: Children with LGG characterized by a BRAF truncated fusion (KIAA1549 and similar translocations). S2: Children with NF1 and LGG. S 3: Children with tumors involving the Ras/Raf pathway not included in strata 1 or 2.

Drug: MEK162

Target Validation

EXPERIMENTAL

Patients eligible for phase 2 (any stratum) for whom tumor biopsy or resection is clinically indicated may be enrolled on the target validation arm. Patients will receive MEK162 for 7 to 21 days prior to their surgery. Tumor sample will be analyzed for drug concentration and target inhibition.

Drug: MEK162

Interventions

MEK162 DRUG

• 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

Also known as: ARRY 438162, Binimetinib

Phase 1; Phase 2; Target Validation

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may not qualify if:

• Patients with any of the following characteristics will not be eligible:
• Patients for whom other curative or established standard-of-care therapeutic options with acceptable morbidity exist.
• Patients with any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy.
• History of Gilbert's syndrome
• Patients receiving any other anticancer or experimental drug therapy.
• Use of hematopoietic growth factors within 2 weeks prior to initiation of therapy.
• Any other investigational agents within 2 weeks or ≤ 3 half-lives (whichever is longer) before start of study therapy.
• Patients who have undergone surgery ≤ 3 weeks or who have not recovered from side effects of this procedure prior to receiving study drug.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, impaired gastrointestinal function, or psychiatric illness/social situations that would limit compliance with study requirements.
• History or current evidence of retinal vein occlusion (RVO) or predisposing factors to RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes).
• History of retinal degenerative disease
• Prior therapy with a MEK inhibitor
• Impairment of gastrointestinal function (e.g., active ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome)
• Patients who have a neuromuscular disorder that is associated with elevated CK (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy).
• Patients with uncontrolled hypertension

Sponsors & Collaborators

• Children's Hospital Los Angeles: lead
• Dana-Farber Cancer Institute: collaborator

Study Sites (15)

Children's Hospital of Alabama

Birmingham, Alabama, 35233, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Children's Hospital of Colorado

Aurora, Colorado, 80045, United States

Location

Children's National Heath Systems

Washington D.C., District of Columbia, 20010, United States

Location

Nicklaus Children's Hospital

Miami, Florida, 33155, United States

Location

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Children's Hospitals and Clinics of Minnesota-Minneapolis

Minneapolis, Minnesota, 55404, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

New York University

New York, New York, 10016, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

University of Texas Southwestern Medical

Dallas, Texas, 75390, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98145, United States

Location

MeSH Terms

Conditions

Brain Neoplasms; Soft Tissue Neoplasms

Interventions

binimetinib

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Results Point of Contact

• Title: Dr. Nathan Robison
• Organization: Children's Hospital Los Angeles

mek162@chla.usc.edu

323.361.2121

Study Officials

• Nathan Robison, MD

  CHLA

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Director of Inpatient Services, Attending Neuro-Oncologist, Associate Professor

Study Record Dates

• First Submitted: October 9, 2014
• First Posted: November 7, 2014
• Study Start: May 4, 2016
• Primary Completion: November 2, 2022
• Study Completion: August 1, 2025
• Last Updated: October 7, 2025
• Results First Posted: October 7, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (15)