Study of MEK162 for Children With Low-Grade Gliomas

September 17, 2025 updated by: Nathan Robison, M.D., Children's Hospital Los Angeles

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
105

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Children's Hospital of Alabama
    • California
      • Los Angeles, California, United States, 90027
        • Children's Hospital Los Angeles
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Children's Hospital of Colorado
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20010
        • Children's National Heath Systems
    • Florida
      • Miami, Florida, United States, 33155
        • Nicklaus Children's Hospital
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Children's Healthcare of Atlanta
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins University
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana Farber Cancer Institute
    • Minnesota
      • Minneapolis, Minnesota, United States, 55404
        • Children's Hospitals and Clinics of Minnesota-Minneapolis
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Washington University School of Medicine
    • New York
      • New York, New York, United States, 10016
        • New York University
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health and Science University
    • Texas
      • Dallas, Texas, United States, 75390
        • University of Texas Southwestern Medical
      • Houston, Texas, United States, 77030
        • Texas Children's Hospital
    • Washington
      • Seattle, Washington, United States, 98145
        • Seattle Children's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

1 year to 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Patients with recurrent or progressive disease, as defined in the following three strata below, will be eligible. For eligibility determination, tumor imaging from at least two time-points must be available to document radiographic progression or recurrence. Patients with non-progressive refractory tumors will not be eligible.

  • Stratum 1: patients with LGG with a BRAF truncated fusion that is measurable in at least two dimensions on imaging.
  • Stratum 2: patients with NF1 and LGG that is measurable in at least two dimensions on imaging.
  • Stratum 3: Pediatric patients with a recurrent or progressive tumor thought to involve the Ras/Raf/ERK pathway but not included in strata 1 or 2 that is measurable in at least two dimensions on imaging. 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 documented activating BRAF, NRAS, or KRAS mutation.
  • Stratum 4 (surgical arm, target validation): Patients who meet criteria for stratum 1, 2, or 3 for whom tumor biopsy and/or resection is clinically indicated.
  • Tumor tissue for correlative studies must be available for all patients except those with NF1 and LGG (stratum 2) or any patient with optic pathway glioma (stratum 2 or 3), for whom tumor tissue is optional.
  • Patients must have received at least one prior chemotherapy or radiation regimen prior to progression.
  • At the time of enrollment, at least 6 weeks must have elapsed since the last dose of any nitrosourea, and the longer of 2 weeks or 3 half-lives must have elapsed since the last dose of any other tumor-directed medication. or biologic therapy.
  • At least 3 months must have elapsed since the last dose of irradiation to the target tumor(s) at the time of enrollment.
  • Patients must be >1 year and <18 years old.
  • Performance Score using the Karnofsky Performance Scale (patients > 12 years old) or Lansky Play - Performance Scale (patients ≤ 12 years old) must be ≥ 60 assessed within two weeks prior to enrollment.

  • Participants must have normal organ and marrow function as defined below within two weeks prior to enrollment:

    • Absolute neutrophil count > 1,000/mcL
    • Platelets > 75,000/mcL and > 7 days since last platelet transfusion. Hemoglobin > 9 gm/dL and > 7 days since last red blood cell transfusion
    • Not refractory to red cell or platelet transfusions
    • Hepatic: Total bilirubin ≤ 1.5 times the upper limit of normal; SGPT (ALT) and SGOT (AST) < 3 times the institutional upper limit of normal
    • Renal: Serum creatinine which is less than 1.5 time the upper limit of institutional normal for age or GFR > 70 ml/min/1.73m2
    • QTc interval < 450ms
    • Left ventricular ejection fraction (LVEF) > 50% as determined by an echocardiogram
  • Female patients of childbearing potential must have negative serum or urine pregnancy test within 72 hours of the first dose of MEK162. Patient must not be pregnant or breast-feeding. Patients of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study and for 30 days following cessation of treatment.
  • Patient must be able to take oral/enteral medication.
  • Patient, parent, or legal guardian must be able to understand and willing to provide informed consent.
  • Patients must have recovered from the effects of prior therapy.

Exclusion Criteria

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

Inclusion of Women, Minorities, and Other Underrepresented Populations This protocol is open to males and females of all races. See Inclusion Criteria above regarding specific eligibility requirements for female and male patients of child-bearing or child-fathering potential, respectively.

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?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Phase 1
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
• 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
Other Names:
  • ARRY 438162
  • Binimetinib
Experimental: Phase 2
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
• 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
Other Names:
  • ARRY 438162
  • Binimetinib
Experimental: Target Validation
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
• 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
Other Names:
  • ARRY 438162
  • Binimetinib

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Best Overall Response Rate (Strata 1 and 2)
Time Frame: 48 weeks
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)
Time Frame: 48 weeks
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

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Survival
Time Frame: Study duration (up to 3 years)
12-month progression-free and overall survival (strata 1 and 2)
Study duration (up to 3 years)

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Stratum 3 Response Rate
Time Frame: Study duration (up to 3 years)
Response rate for patients in stratum 3 (other tumors with known or presumed activation of the ras/raf/MEK/ERK pathway, not included in strata 1 or 2).
Study duration (up to 3 years)
Tumor response as a function of BRAF tumoral genotype
Time Frame: Study duration (up to 3 years)
Tumor response as a function of BRAF tumoral genotype.
Study duration (up to 3 years)
Target Validation (Intra-tumoral MEK162 concentration, and intra-tumoral inhibition of downstream mediators of the ras/raf/MEK/ERK pathway (e.g., pERK).
Time Frame: Study duration (up to 3 years)
Target Validation: Intra-tumoral MEK162 concentration, and intra-tumoral inhibition of downstream mediators of the ras/raf/MEK/ERK pathway (e.g., pERK).
Study duration (up to 3 years)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Children's Hospital Los Angeles

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Dana-Farber Cancer Institute

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Nathan Robison, MD, CHLA

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 4, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 2, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 9, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 6, 2014

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 7, 2014

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 7, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 17, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CHLA-15-00146

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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