Study of MEK162 for Children With Low-Grade Gliomas
- Conditions
- Low-Grade GliomasSoft Tissue NeoplasmsMalignant Neoplasms, Brain
- Interventions
- Registration Number
- NCT02285439
- Lead Sponsor
- Children's Hospital Los Angeles
- 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.
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 105
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Phase 1 MEK162 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. Phase 2 MEK162 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. Target Validation MEK162 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.
- Primary Outcome Measures
Name Time Method Response rate Study duration (up to 3 years) Phase 2: Response rate (strata 1 and 2)
- Secondary Outcome Measures
Name Time Method Survival Study duration (up to 3 years) 12-month progression-free and overall survival (strata 1 and 2)
Trial Locations
- Locations (15)
University of Texas Southwestern Medical
🇺🇸Dallas, Texas, United States
Texas Children's Hospital
🇺🇸Houston, Texas, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
Nicklaus Children's Hospital
🇺🇸Miami, Florida, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Children's National Heath Systems
🇺🇸Washington, District of Columbia, United States
Children's Healthcare of Atlanta
🇺🇸Atlanta, Georgia, United States
Children's Hospital of Alabama
🇺🇸Birmingham, Alabama, United States
Children's Hospital of Colorado
🇺🇸Aurora, Colorado, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
Children's Hospitals and Clinics of Minnesota-Minneapolis
🇺🇸Minneapolis, Minnesota, United States
New York University
🇺🇸New York, New York, United States