Dabrafenib Combined With Trametinib After Radiation Therapy in Treating Patients With Newly-Diagnosed High-Grade Glioma

April 24, 2024 updated by: National Cancer Institute (NCI)

A Phase 2 Study of Dabrafenib (NSC# 763760) With Trametinib (NSC# 763093) After Local Irradiation in Newly-Diagnosed BRAF V600-Mutant High-Grade Glioma (HGG)

This phase II trial studies how well the combination of dabrafenib and trametinib works after radiation therapy in children and young adults with high grade glioma who have a genetic change called BRAF V600 mutation. Radiation therapy uses high energy rays to kill tumor cells and reduce the size of tumors. Dabrafenib and trametinib may stop the growth of tumor cells by blocking BRAF and MEK, respectively, which are enzymes that tumor cells need for their growth. Giving dabrafenib with trametinib after radiation therapy may work better than treatments used in the past in patients with newly-diagnosed BRAF V600-mutant high-grade glioma.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVE:

I. To estimate the event-free survival (EFS) distribution for newly-diagnosed patients with BRAF^V600-mutant high-grade glioma (HGG) without H3 K27M mutations excluding anaplastic pleomorphic xanthoastrocytoma (aPXA) and anaplastic ganglioglioma (aGG) treated with radiation therapy followed by a maintenance combination of dabrafenib mesylate (dabrafenib) and trametinib dimethyl sulfoxide (trametinib) and to compare this EFS to contemporary historical controls.

SECONDARY OBJECTIVES:

I. To describe the overall survival (OS) distribution for newly-diagnosed patients with BRAF^V600-mutant HGG without H3 K27M mutations excluding aPXA and aGG treated with radiation therapy followed by a maintenance combination of dabrafenib and trametinib.

II. To describe the EFS and overall survival (OS) distribution for newly-diagnosed patients with BRAF^V600E-mutant aPXA and aGG without H3 K27M mutations treated with radiation therapy followed by a maintenance combination of dabrafenib and trametinib.

III. To describe the EFS and overall survival (OS) distribution for newly-diagnosed patients with BRAF^V600E-mutant HGG including aPXA and aGG with H3 K27M mutations treated with radiation therapy followed by a maintenance combination of dabrafenib and trametinib.

IV. To define and evaluate the toxicities of combination therapy with dabrafenib and trametinib after radiation therapy in newly-diagnosed patients with HGG.

EXPLORATORY OBJECTIVE:

I. To bank tumor specimens and body fluids (blood, urine and cerebrospinal fluid) for future studies.

OUTLINE:

Patients undergo standardized local radiation therapy (RT) 5 days a week (Monday-Friday) for 6-7 weeks. Four weeks after completion of RT, patients receive dabrafenib mesylate orally (PO) twice daily (BID) and trametinib dimethyl sulfoxide PO once daily (QD) on days 1-28 of each cycle. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a magnetic resonance imaging (MRI) at baseline, on day 1 of cycles 1, 3, 5, 7, 11, 14, 17, 20, and 23 while on treatment, then at time of relapse, every 3 months for year 1, every 4 months for year 3, every 6 months for year 3, and annually for years 4-5. Patients may also undergo lumbar puncture for cerebral spinal fluid (CSF) testing during treatment. Patients also undergo collection of blood on study.

After completion of study treatment, patients are followed up at disease relapse, every 3 months for year 1, every 4 months for year 2, every 6 months for year 3, then annually for years 4-5.

Study Type

Interventional

Enrollment (Estimated)

58

Phase

  • Phase 2

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

  • Puerto Rico
      • Caguas, Puerto Rico, 00726
        • Suspended
        • HIMA San Pablo Oncologic Hospital
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Suspended
        • Children's Hospital of Alabama
    • Arizona
      • Mesa, Arizona, United States, 85202
        • Recruiting
        • Banner Children's at Desert
        • Contact:
          • Site Public Contact
          • Phone Number: 480-412-3100
        • Principal Investigator:
          • Joseph C. Torkildson
      • Phoenix, Arizona, United States, 85016
        • Recruiting
        • Phoenix Childrens Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 602-546-0920
        • Principal Investigator:
          • Lindsey M. Hoffman
    • Arkansas
      • Little Rock, Arkansas, United States, 72202-3591
        • Recruiting
        • Arkansas Children's Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 501-364-7373
        • Principal Investigator:
          • David L. Becton
    • California
      • Downey, California, United States, 90242
        • Recruiting
        • Kaiser Permanente Downey Medical Center
        • Contact:
          • Site Public Contact
          • Phone Number: 626-564-3455
        • Principal Investigator:
          • Hung N. Tran
      • Loma Linda, California, United States, 92354
        • Recruiting
        • Loma Linda University Medical Center
        • Contact:
          • Site Public Contact
          • Phone Number: 909-558-4050
        • Principal Investigator:
          • Albert Kheradpour
      • Long Beach, California, United States, 90806
        • Recruiting
        • Miller Children's and Women's Hospital Long Beach
        • Contact:
          • Site Public Contact
          • Phone Number: 562-933-5600
        • Principal Investigator:
          • Jacqueline N. Casillas
      • Los Angeles, California, United States, 90027
        • Recruiting
        • Children's Hospital Los Angeles
        • Contact:
          • Site Public Contact
          • Phone Number: 323-361-4110
        • Principal Investigator:
          • Tom B. Davidson
      • Los Angeles, California, United States, 90048
        • Recruiting
        • Cedars Sinai Medical Center
        • Contact:
          • Site Public Contact
          • Phone Number: 310-423-8965
        • Principal Investigator:
          • Fataneh (Fae) Majlessipour
      • Oakland, California, United States, 94611
        • Recruiting
        • Kaiser Permanente-Oakland
        • Contact:
          • Site Public Contact
          • Phone Number: 877-642-4691
          • Email: Kpoct@kp.org
        • Principal Investigator:
          • Aarati V. Rao
      • Orange, California, United States, 92868
        • Recruiting
        • Children's Hospital of Orange County
        • Contact:
        • Principal Investigator:
          • Elyssa M. Rubin
      • Palo Alto, California, United States, 94304
        • Recruiting
        • Lucile Packard Children's Hospital Stanford University
        • Contact:
        • Principal Investigator:
          • Jay Michael S. Balagtas
      • Sacramento, California, United States, 95817
        • Active, not recruiting
        • University of California Davis Comprehensive Cancer Center
      • San Francisco, California, United States, 94158
        • Recruiting
        • UCSF Medical Center-Mission Bay
        • Contact:
        • Principal Investigator:
          • Alyssa T. Reddy
      • Torrance, California, United States, 90502
        • Active, not recruiting
        • Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Recruiting
        • Children's Hospital Colorado
        • Contact:
        • Principal Investigator:
          • Kathleen M. Dorris
    • Connecticut
      • Hartford, Connecticut, United States, 06106
        • Recruiting
        • Connecticut Children's Medical Center
        • Contact:
          • Site Public Contact
          • Phone Number: 860-545-9981
        • Principal Investigator:
          • Michael S. Isakoff
      • New Haven, Connecticut, United States, 06520
        • Recruiting
        • Yale University
        • Contact:
        • Principal Investigator:
          • Farzana Pashankar
    • Delaware
      • Wilmington, Delaware, United States, 19803
        • Recruiting
        • Alfred I duPont Hospital for Children
        • Contact:
        • Principal Investigator:
          • Scott M. Bradfield
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Active, not recruiting
        • MedStar Georgetown University Hospital
      • Washington, District of Columbia, United States, 20010
        • Recruiting
        • Children's National Medical Center
        • Principal Investigator:
          • Jeffrey S. Dome
        • Contact:
    • Florida
      • Fort Myers, Florida, United States, 33908
        • Recruiting
        • Golisano Children's Hospital of Southwest Florida
        • Contact:
        • Principal Investigator:
          • Emad K. Salman
      • Gainesville, Florida, United States, 32610
        • Recruiting
        • University of Florida Health Science Center - Gainesville
        • Contact:
        • Principal Investigator:
          • William B. Slayton
      • Hollywood, Florida, United States, 33021
        • Recruiting
        • Memorial Regional Hospital/Joe DiMaggio Children's Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 954-265-1847
          • Email: OHR@mhs.net
        • Principal Investigator:
          • Iftikhar Hanif
      • Jacksonville, Florida, United States, 32207
        • Recruiting
        • Nemours Children's Clinic-Jacksonville
        • Contact:
        • Principal Investigator:
          • Scott M. Bradfield
      • Miami, Florida, United States, 33155
        • Recruiting
        • Nicklaus Children's Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 888-624-2778
        • Principal Investigator:
          • Ziad A. Khatib
      • Miami, Florida, United States, 33136
        • Recruiting
        • University of Miami Miller School of Medicine-Sylvester Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 305-243-2647
        • Principal Investigator:
          • Julio C. Barredo
      • Orlando, Florida, United States, 32806
        • Recruiting
        • Arnold Palmer Hospital for Children
        • Contact:
        • Principal Investigator:
          • Amy A. Smith
      • Orlando, Florida, United States, 32827
        • Recruiting
        • Nemours Children's Hospital
        • Contact:
        • Principal Investigator:
          • Scott M. Bradfield
      • Orlando, Florida, United States, 32803
        • Recruiting
        • AdventHealth Orlando
        • Contact:
        • Principal Investigator:
          • Fouad M. Hajjar
      • Saint Petersburg, Florida, United States, 33701
        • Recruiting
        • Johns Hopkins All Children's Hospital
        • Contact:
        • Principal Investigator:
          • Stacie L. Stapleton
      • Tampa, Florida, United States, 33606
        • Recruiting
        • Tampa General Hospital
        • Contact:
        • Principal Investigator:
          • Andrew J. Galligan
      • Tampa, Florida, United States, 33607
        • Recruiting
        • Saint Joseph's Hospital/Children's Hospital-Tampa
        • Contact:
        • Principal Investigator:
          • Don E. Eslin
      • West Palm Beach, Florida, United States, 33407
        • Recruiting
        • Saint Mary's Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 561-881-2815
        • Principal Investigator:
          • Matthew D. Ramirez
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Children's Healthcare of Atlanta - Egleston
        • Contact:
        • Principal Investigator:
          • Tobey J. MacDonald
      • Savannah, Georgia, United States, 31404
        • Recruiting
        • Memorial Health University Medical Center
        • Contact:
        • Principal Investigator:
          • Andrew L. Pendleton
    • Hawaii
      • Honolulu, Hawaii, United States, 96826
        • Recruiting
        • Kapiolani Medical Center for Women and Children
        • Contact:
          • Site Public Contact
          • Phone Number: 808-983-6090
        • Principal Investigator:
          • Wade T. Kyono
    • Idaho
      • Boise, Idaho, United States, 83712
        • Recruiting
        • Saint Luke's Cancer Institute - Boise
        • Principal Investigator:
          • Martha M. Pacheco
        • Contact:
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Recruiting
        • Lurie Children's Hospital-Chicago
        • Contact:
          • Site Public Contact
          • Phone Number: 773-880-4562
        • Principal Investigator:
          • Angela J. Waanders
      • Chicago, Illinois, United States, 60612
        • Active, not recruiting
        • University of Illinois
      • Chicago, Illinois, United States, 60637
        • Recruiting
        • University of Chicago Comprehensive Cancer Center
        • Contact:
        • Principal Investigator:
          • Wendy S. Darlington
      • Peoria, Illinois, United States, 61637
        • Recruiting
        • Saint Jude Midwest Affiliate
        • Contact:
          • Site Public Contact
          • Phone Number: 888-226-4343
        • Principal Investigator:
          • Prerna Kumar
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Recruiting
        • Riley Hospital for Children
        • Contact:
          • Site Public Contact
          • Phone Number: 800-248-1199
        • Principal Investigator:
          • Sandeep Batra
      • Indianapolis, Indiana, United States, 46260
        • Recruiting
        • Ascension Saint Vincent Indianapolis Hospital
        • Contact:
        • Principal Investigator:
          • Jessica F. Goodman
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Recruiting
        • University of Iowa/Holden Comprehensive Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 800-237-1225
        • Principal Investigator:
          • David S. Dickens
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • Recruiting
        • University of Kentucky/Markey Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 859-257-3379
        • Principal Investigator:
          • James T. Badgett
      • Louisville, Kentucky, United States, 40202
        • Recruiting
        • Norton Children's Hospital
        • Contact:
        • Principal Investigator:
          • Ashok B. Raj
    • Louisiana
      • New Orleans, Louisiana, United States, 70118
        • Recruiting
        • Children's Hospital New Orleans
        • Contact:
        • Principal Investigator:
          • Lolie C. Yu
      • New Orleans, Louisiana, United States, 70121
        • Recruiting
        • Ochsner Medical Center Jefferson
        • Contact:
        • Principal Investigator:
          • Craig Lotterman
    • Maine
      • Bangor, Maine, United States, 04401
        • Recruiting
        • Eastern Maine Medical Center
        • Contact:
          • Site Public Contact
          • Phone Number: 207-973-4274
        • Principal Investigator:
          • Daniel L. Callaway
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Recruiting
        • Johns Hopkins University/Sidney Kimmel Cancer Center
        • Contact:
        • Principal Investigator:
          • Kenneth J. Cohen
      • Bethesda, Maryland, United States, 20889-5600
        • Recruiting
        • Walter Reed National Military Medical Center
        • Contact:
          • Site Public Contact
          • Phone Number: 301-319-2100
        • Principal Investigator:
          • Allen I. Stering
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 877-726-5130
        • Principal Investigator:
          • David H. Ebb
      • Boston, Massachusetts, United States, 02215
        • Recruiting
        • Dana-Farber Cancer Institute
        • Contact:
          • Site Public Contact
          • Phone Number: 877-442-3324
        • Principal Investigator:
          • Susan N. Chi
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • C S Mott Children's Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 800-865-1125
        • Principal Investigator:
          • Carl J. Koschmann
      • Detroit, Michigan, United States, 48201
      • Grand Rapids, Michigan, United States, 49503
        • Recruiting
        • Helen DeVos Children's Hospital at Spectrum Health
        • Principal Investigator:
          • Kathleen J. Yost
        • Contact:
      • Kalamazoo, Michigan, United States, 49007
        • Recruiting
        • Bronson Methodist Hospital
        • Contact:
        • Principal Investigator:
          • Kathleen J. Yost
      • Royal Oak, Michigan, United States, 48073
        • Recruiting
        • Beaumont Children's Hospital-Royal Oak
        • Contact:
          • Site Public Contact
          • Phone Number: 248-551-7695
        • Principal Investigator:
          • Laura K. Gowans
    • Minnesota
      • Minneapolis, Minnesota, United States, 55404
        • Recruiting
        • Children's Hospitals and Clinics of Minnesota - Minneapolis
        • Principal Investigator:
          • Michael K. Richards
        • Contact:
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic in Rochester
        • Contact:
          • Site Public Contact
          • Phone Number: 855-776-0015
        • Principal Investigator:
          • Jonathan D. Schwartz
    • Mississippi
      • Jackson, Mississippi, United States, 39216
        • Recruiting
        • University of Mississippi Medical Center
        • Principal Investigator:
          • Betty L. Herrington
        • Contact:
          • Site Public Contact
          • Phone Number: 601-815-6700
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • Recruiting
        • Children's Mercy Hospitals and Clinics
        • Contact:
          • Site Public Contact
          • Phone Number: 816-302-6808
          • Email: rryan@cmh.edu
        • Principal Investigator:
          • Keith J. August
      • Saint Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University School of Medicine
        • Contact:
        • Principal Investigator:
          • Andrew S. Cluster
      • Saint Louis, Missouri, United States, 63104
        • Recruiting
        • Cardinal Glennon Children's Medical Center
        • Contact:
          • Site Public Contact
          • Phone Number: 314-268-4000
        • Principal Investigator:
          • William S. Ferguson
      • Saint Louis, Missouri, United States, 63141
        • Recruiting
        • Mercy Hospital Saint Louis
        • Contact:
          • Site Public Contact
          • Phone Number: 314-251-7066
        • Principal Investigator:
          • Robin D. Hanson
    • Nebraska
      • Omaha, Nebraska, United States, 68114
        • Recruiting
        • Children's Hospital and Medical Center of Omaha
        • Contact:
          • Site Public Contact
          • Phone Number: 402-955-3949
        • Principal Investigator:
          • Jill C. Beck
      • Omaha, Nebraska, United States, 68198
        • Recruiting
        • University of Nebraska Medical Center
        • Contact:
        • Principal Investigator:
          • Jill C. Beck
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Recruiting
        • Hackensack University Medical Center
        • Contact:
          • Site Public Contact
          • Phone Number: 201-996-2879
        • Principal Investigator:
          • Derek R. Hanson
      • Morristown, New Jersey, United States, 07960
        • Recruiting
        • Morristown Medical Center
        • Contact:
          • Site Public Contact
          • Phone Number: 973-971-5900
        • Principal Investigator:
          • Kathryn L. Laurie
      • New Brunswick, New Jersey, United States, 08903
        • Recruiting
        • Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
        • Principal Investigator:
          • Scott Moerdler
        • Contact:
          • Site Public Contact
          • Phone Number: 732-235-8675
      • Newark, New Jersey, United States, 07112
        • Recruiting
        • Newark Beth Israel Medical Center
        • Contact:
        • Principal Investigator:
          • Teena Bhatla
      • Paterson, New Jersey, United States, 07503
        • Recruiting
        • Saint Joseph's Regional Medical Center
        • Contact:
        • Principal Investigator:
          • Alissa Kahn
    • New Mexico
      • Albuquerque, New Mexico, United States, 87102
        • Recruiting
        • University of New Mexico Cancer Center
        • Contact:
        • Principal Investigator:
          • Jessica M. Valdez
    • New York
      • Albany, New York, United States, 12208
        • Recruiting
        • Albany Medical Center
        • Contact:
          • Site Public Contact
          • Phone Number: 518-262-5513
        • Principal Investigator:
          • Lauren R. Weintraub
      • Bronx, New York, United States, 10467
        • Recruiting
        • Montefiore Medical Center - Moses Campus
        • Contact:
        • Principal Investigator:
          • Alice Lee
      • Buffalo, New York, United States, 14263
        • Recruiting
        • Roswell Park Cancer Institute
        • Contact:
        • Principal Investigator:
          • Clare J. Twist
      • New Hyde Park, New York, United States, 11040
        • Recruiting
        • The Steven and Alexandra Cohen Children's Medical Center of New York
        • Contact:
          • Site Public Contact
          • Phone Number: 718-470-3460
        • Principal Investigator:
          • Julie I. Krystal
      • New York, New York, United States, 10032
        • Recruiting
        • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
        • Principal Investigator:
          • Nobuko Hijiya
        • Contact:
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan Kettering Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 212-639-7592
        • Principal Investigator:
          • Sameer Farouk Sait
      • Syracuse, New York, United States, 13210
        • Recruiting
        • State University of New York Upstate Medical University
        • Contact:
          • Site Public Contact
          • Phone Number: 315-464-5476
        • Principal Investigator:
          • Philip M. Monteleone
    • North Carolina
      • Asheville, North Carolina, United States, 28801
      • Charlotte, North Carolina, United States, 28203
        • Recruiting
        • Carolinas Medical Center/Levine Cancer Institute
        • Contact:
          • Site Public Contact
          • Phone Number: 800-804-9376
        • Principal Investigator:
          • Joel A. Kaplan
      • Charlotte, North Carolina, United States, 28204
        • Recruiting
        • Novant Health Presbyterian Medical Center
        • Contact:
        • Principal Investigator:
          • Jessica A. Bell
      • Greenville, North Carolina, United States, 27834
        • Recruiting
        • East Carolina University
        • Contact:
        • Principal Investigator:
          • Andrea R. Whitfield
      • Winston-Salem, North Carolina, United States, 27157
        • Recruiting
        • Wake Forest University Health Sciences
        • Contact:
          • Site Public Contact
          • Phone Number: 336-713-6771
        • Principal Investigator:
          • Thomas W. McLean
    • North Dakota
      • Fargo, North Dakota, United States, 58122
    • Ohio
      • Akron, Ohio, United States, 44308
        • Recruiting
        • Children's Hospital Medical Center of Akron
        • Contact:
          • Site Public Contact
          • Phone Number: 330-543-3193
        • Principal Investigator:
          • Erin Wright
      • Cincinnati, Ohio, United States, 45229
        • Recruiting
        • Cincinnati Children's Hospital Medical Center
        • Contact:
        • Principal Investigator:
          • Peter M. de Blank
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • Cleveland Clinic Foundation
        • Contact:
        • Principal Investigator:
          • Rabi Hanna
      • Cleveland, Ohio, United States, 44106
        • Recruiting
        • Rainbow Babies and Childrens Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 216-844-5437
        • Principal Investigator:
          • Duncan S. Stearns
      • Columbus, Ohio, United States, 43205
      • Dayton, Ohio, United States, 45404
        • Recruiting
        • Dayton Children's Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 800-228-4055
        • Principal Investigator:
          • Mukund G. Dole
      • Toledo, Ohio, United States, 43606
        • Recruiting
        • ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
        • Contact:
        • Principal Investigator:
          • Jamie L. Dargart
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Recruiting
        • University of Oklahoma Health Sciences Center
        • Contact:
        • Principal Investigator:
          • Rene Y. McNall-Knapp
    • Oregon
      • Portland, Oregon, United States, 97227
        • Recruiting
        • Legacy Emanuel Children's Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 503-413-2560
        • Principal Investigator:
          • Jason M. Glover
      • Portland, Oregon, United States, 97239
        • Recruiting
        • Oregon Health and Science University
        • Contact:
        • Principal Investigator:
          • Linda C. Stork
    • Pennsylvania
      • Allentown, Pennsylvania, United States, 18103
        • Recruiting
        • Lehigh Valley Hospital-Cedar Crest
        • Contact:
        • Principal Investigator:
          • Jacob A. Troutman
      • Hershey, Pennsylvania, United States, 17033
        • Recruiting
        • Penn State Children's Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 717-531-6012
        • Principal Investigator:
          • Lisa M. McGregor
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • Children's Hospital of Philadelphia
        • Contact:
        • Principal Investigator:
          • Jane E. Minturn
      • Pittsburgh, Pennsylvania, United States, 15224
        • Recruiting
        • Children's Hospital of Pittsburgh of UPMC
        • Contact:
        • Principal Investigator:
          • James T. Felker
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Recruiting
        • Rhode Island Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 401-444-1488
        • Principal Investigator:
          • Jennifer J. Welch
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Recruiting
        • Medical University of South Carolina
        • Contact:
        • Principal Investigator:
          • Jacqueline M. Kraveka
      • Columbia, South Carolina, United States, 29203
        • Recruiting
        • Prisma Health Richland Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 864-241-6251
        • Principal Investigator:
          • Stuart L. Cramer
      • Greenville, South Carolina, United States, 29605
        • Recruiting
        • BI-LO Charities Children's Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 864-241-6251
        • Principal Investigator:
          • Aniket Saha
    • Tennessee
      • Knoxville, Tennessee, United States, 37916
        • Recruiting
        • East Tennessee Childrens Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 865-541-8266
        • Principal Investigator:
          • Susan E. Spiller
      • Memphis, Tennessee, United States, 38105
        • Recruiting
        • Saint Jude Children's Research Hospital
        • Contact:
        • Principal Investigator:
          • Emily Hanzlik
      • Nashville, Tennessee, United States, 37232
        • Recruiting
        • Vanderbilt University/Ingram Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 800-811-8480
        • Principal Investigator:
          • Devang J. Pastakia
      • Nashville, Tennessee, United States, 37203
        • Recruiting
        • The Children's Hospital at TriStar Centennial
        • Contact:
          • Site Public Contact
          • Phone Number: 615-342-1919
        • Principal Investigator:
          • Jennifer A. Domm
    • Texas
      • Austin, Texas, United States, 78723
        • Recruiting
        • Dell Children's Medical Center of Central Texas
        • Contact:
        • Principal Investigator:
          • Shannon M. Cohn
      • Dallas, Texas, United States, 75390
        • Recruiting
        • UT Southwestern/Simmons Cancer Center-Dallas
        • Contact:
        • Principal Investigator:
          • Daniel C. Bowers
      • Dallas, Texas, United States, 75230
        • Recruiting
        • Medical City Dallas Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 972-566-5588
        • Principal Investigator:
          • Stanton C. Goldman
      • Fort Worth, Texas, United States, 76104
      • Houston, Texas, United States, 77030
        • Recruiting
        • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 713-798-1354
          • Email: burton@bcm.edu
        • Principal Investigator:
          • Patricia A. Baxter
      • San Antonio, Texas, United States, 78207
        • Recruiting
        • Children's Hospital of San Antonio
        • Contact:
        • Principal Investigator:
          • Timothy C. Griffin
      • San Antonio, Texas, United States, 78229
        • Recruiting
        • University of Texas Health Science Center at San Antonio
        • Contact:
        • Principal Investigator:
          • Shafqat Shah
      • Temple, Texas, United States, 76508
        • Recruiting
        • Scott and White Memorial Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 254-724-5407
        • Principal Investigator:
          • Nicholas W. McGregor
    • Utah
      • Salt Lake City, Utah, United States, 84113
        • Recruiting
        • Primary Children's Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 801-585-5270
        • Principal Investigator:
          • Priya Chan
    • Virginia
      • Charlottesville, Virginia, United States, 22908
      • Norfolk, Virginia, United States, 23507
        • Recruiting
        • Children's Hospital of The King's Daughters
        • Contact:
        • Principal Investigator:
          • Eric J. Lowe
    • Washington
      • Seattle, Washington, United States, 98105
        • Recruiting
        • Seattle Children's Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 866-987-2000
        • Principal Investigator:
          • Sarah E. Leary
      • Spokane, Washington, United States, 99204
        • Recruiting
        • Providence Sacred Heart Medical Center and Children's Hospital
        • Contact:
        • Principal Investigator:
          • Judy L. Felgenhauer
      • Tacoma, Washington, United States, 98405
        • Recruiting
        • Mary Bridge Children's Hospital and Health Center
        • Contact:
        • Principal Investigator:
          • Robert G. Irwin
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • Recruiting
        • University of Wisconsin Carbone Cancer Center
        • Principal Investigator:
          • Kenneth B. De Santes
        • Contact:
      • Marshfield, Wisconsin, United States, 54449
      • Milwaukee, Wisconsin, United States, 53226
        • Recruiting
        • Children's Hospital of Wisconsin
        • Contact:
        • Principal Investigator:
          • Sarah Rumler

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

Ages Eligible for Study

1 year to 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • PRE-ENROLLMENT ELIGIBILITY SCREENING: Patients must be =< 25 years of age at the time of enrollment on APEC14B1 Part A CNS/HGG pre-enrollment eligibility screening.

    • Note: This required age range applies to the pre-enrollment eligibility screening for all HGG patients. Individual treatment protocols may have different age criteria.
  • PRE-ENROLLMENT ELIGIBILITY SCREENING: Patient is suspected of having localized newly-diagnosed HGG, excluding metastatic disease.
  • PRE-ENROLLMENT ELIGIBILITY SCREENING: Patient and/or their parents or legal guardians have signed informed consent for eligibility screening on APEC14B1 Part A.

  • PRE-ENROLLMENT ELIGIBILITY SCREENING: The specimens obtained at the time of diagnostic biopsy or surgery must be submitted through APEC14B1 as soon as possible (ASAP), preferably within 5 calendar days of the procedure.

    • Please note: See the APEC14B1 Manual of Procedures for a full list of detailed instructions for submitting required materials and for shipping details.
  • Patients must be >= 3 years and =< 25 years of age at the time of enrollment.

  • Patients must have eligibility confirmed by Rapid Central Pathology and Molecular Screening Reviews performed on APEC14B1

    • Newly diagnosed high-grade glioma with BRAF^V600-mutation
    • Results for H3 K27M by immunohistochemistry (IHC) or sequencing
    • Histologically confirmed high-grade glioma (World Health Organization [WHO] grade III or IV) including but not limited to: anaplastic astrocytoma (AA), anaplastic pleomorphic xanthoastrocytoma (aPXA), anaplastic gangliogliomas (aGG), glioblastoma (GB), and high-grade astrocytoma, not otherwise specified (NOS).
  • Patients must have had histologic verification of a high-grade glioma diagnosis. CSF cytology by lumbar puncture must be done if clinically indicated and determined to be safe prior to study enrollment. If cytology proves positive, the patient would be considered to have metastatic disease and would, therefore, be ineligible.
  • A pre- and post-operative brain MRI with and without contrast and a baseline spine MRI with contrast must be obtained prior to enrollment. The requirement for a post-operative MRI is waived for patients who undergo biopsy only. If the spine MRI is positive, the patient would be considered to have metastatic disease and would be ineligible.
  • Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2. Use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age.
  • Peripheral absolute neutrophil count (ANC) >= 1000/uL (within 7 days prior to enrollment).
  • Platelet count >= 100,000/uL (transfusion independent) (within 7 days prior to enrollment).
  • Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions) (within 7 days prior to enrollment).
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 (within 7 days prior to enrollment) or

  • A serum creatinine based on age/gender as follows (within 7 days prior to enrollment):

    • Age 3 to < 6 years (Male 0.8 mg/dL, Female 0.8 mg/dL)
    • Age 6 to < 10 years (Male 1 mg/dL, Female 1 mg/dL)
    • Age 10 to < 13 years (Male 1.2 mg/dL, Female 1.2 mg/dL)
    • Age 13 to < 16 years (Male 1.5 mg/dL, Female 1.4 mg/dL)
    • Age >= 16 years (Male 1.7 mg/dL, Female 1.4 mg/dL)
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment), and
  • Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L (within 7 days prior to enrollment). For the purpose of this study, the ULN for SGPT is 45 U/L.
  • Patients with a seizure disorder may be enrolled if their seizures are well controlled while on non-enzyme inducing anticonvulsants permitted on this study.
  • All patients and/or their parents or legal guardians must sign a written informed consent
  • Patients must be enrolled and protocol therapy must be projected to begin no later than 31 days after definitive surgery (day 0). If a biopsy only was performed, the biopsy date will be considered the date of definitive surgery. For patients who have a biopsy or incomplete resection at diagnosis followed by additional surgery, the date of the last resection will be considered the date of definitive surgery.

Exclusion Criteria:

  • Patients with intrinsic brainstem or primary spinal cord tumors will be excluded.
  • Patients with metastatic disease (defined as neuraxis dissemination either by imaging or by cytology) will be excluded.
  • Patients must not have received any prior tumor-directed therapy including chemotherapy, radiation therapy, immunotherapy, or bone marrow transplant for the treatment of HGG other than surgical intervention and/or corticosteroids.
  • Previous treatment with dabrafenib or another RAF inhibitor, trametinib or another MEK inhibitor, or an ERK inhibitor.
  • Patients with a history of a malignancy with confirmed activating RAS mutation.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to dabrafenib, trametinib, and their excipients.
  • Uncontrolled medical conditions (e.g., diabetes mellitus, hypertension, liver disease, or uncontrolled infection), psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol; or unwillingness or inability to follow the procedures required in the protocol.
  • Presence of active gastrointestinal (GI) disease or other condition (e.g., small bowel or large bowel resection) that will interfere significantly with the absorption of drugs.
  • History of hepatitis B virus, or hepatitis C virus infection (patients with laboratory evidence of cleared hepatitis B virus and/or hepatitis C virus may be enrolled).

  • History or current diagnosis of cardiac disease indicating significant risk of safety for patients participating in the study such as uncontrolled or significant cardiac disease, including any of the following:

    • Recent myocardial infarction (within the last 6 months);
    • Uncontrolled congestive heart failure;
    • Unstable angina (within last 6 months);
    • Clinically significant (symptomatic) or known, uncontrolled cardiac arrhythmias (e.g., sustained ventricular tachycardia, and clinically significant second or third degree atrioventricular [AV] block without a pacemaker) except sinus arrhythmia within the past 24 weeks prior to the first dose of study treatment;
    • Coronary angioplasty or stenting (within last 6 months);
    • Intra-cardiac defibrillators;
    • Abnormal cardiac valve morphology (>= grade 2) documented by echocardiogram.
  • Patients with a history or current evidence of retinal vein occlusion (RVO) or central serous retinopathy (CSR), or predisposing factors to RVO or CSR (e.g., uncontrolled glaucoma or ocular hypertension).
  • Patients with presence of interstitial lung disease or pneumonitis.
  • Female patients who are pregnant are ineligible since there is yet no available information regarding human fetal or teratogenic toxicities.
  • Lactating females are not eligible unless they have agreed not to breastfeed their infants for the duration of the study and for 4 months following discontinuation of study therapy.
  • Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained.
  • Sexually active patients of reproductive potential (male or female) are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation and for 4 months following discontinuation of study therapy. Male patients (including those who have had a vasectomy) taking dabrafenib and trametinib combination therapy must use a condom during intercourse while on study and for 16 weeks after stopping treatment, and should not father a child during these periods. Women of childbearing potential should use effective non-hormonal contraception during therapy and for 4 weeks following discontinuation of dabrafenib and at least 4 months following the last dose of trametinib in patients taking combination therapy. Women should be advised that dabrafenib may decrease the efficacy of hormonal contraceptives and an alternate method of contraception, such as barrier methods, should be used.

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (radiation therapy, dabrafenib, trametinib)
Patients undergo standardized local RT 5 days a week (Monday-Friday) for 6-7 weeks. Four weeks after completion of RT, patients receive dabrafenib mesylate PO BID and trametinib dimethyl sulfoxide PO QD on days 1-28 of each cycle. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo MRI at baseline, on day 1 of cycles 1, 3, 5, 7, 11, 14, 17, 20, and 23 while on treatment, then at time of relapse, every 3 months for year 1, every 4 months for year 2, every 6 months for year 3, and annually for years 4-5. Patients may also undergo lumbar puncture for CSF testing during treatment. Patients also undergo collection of blood on study.
Procedure: Biospecimen Collection
Undergo collection of blood
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Drug: Dabrafenib Mesylate
Given PO
Other Names:
  • Dabrafenib Methanesulfonate
  • GSK2118436 Methane Sulfonate Salt
  • GSK2118436B
  • Tafinlar
Procedure: Lumbar Puncture
Undergo lumbar puncture
Other Names:
  • LP
  • Spinal Tap
Procedure: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • MRI
  • Magnetic Resonance
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
  • Magnetic Resonance Imaging (MRI)
  • sMRI
  • Magnetic resonance imaging (procedure)
  • MRIs
  • Structural MRI
Radiation: Radiation Therapy
Undergo RT
Other Names:
  • Cancer Radiotherapy
  • ENERGY_TYPE
  • Irradiate
  • Irradiated
  • Irradiation
  • Radiation
  • Radiation Therapy, NOS
  • Radiotherapeutics
  • Radiotherapy
  • RT
  • Therapy, Radiation
  • Energy Type
Drug: Trametinib Dimethyl Sulfoxide
Given PO
Other Names:
  • Mekinist
  • Meqsel

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Event-free survival (EFS) for stratum 1
Time Frame: From the date of diagnosis until disease progression date, secondary malignant neoplasm occurrence date, death date of any cause, or last follow-up, assessed up to 5 years
The EFS curve for the new treatment cohort (Stratum 1) will be estimated by Kaplan Meier estimates. A 2-sample, 1 sided log-rank test will be used to test whether the EFS distribution is better in new treatment compared with historical control. Calculation of the EFS will be based on the site determination as central review will be performed retrospectively.
From the date of diagnosis until disease progression date, secondary malignant neoplasm occurrence date, death date of any cause, or last follow-up, assessed up to 5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival (OS) for stratum 1, stratum 2, and stratum 3
Time Frame: From the date of diagnosis until death date of any cause or last follow up date, assessed up to 5 years
The OS curve for the new treatment cohort (stratum 1) will be estimated by Kaplan Meier estimates. A 2-sample, 1 sided log-rank test will be used to test whether the OS distribution is better in new treatment compared with historical control. For stratum 2 and stratum 3, Kaplan Meier estimates will be provided for OS distribution.
From the date of diagnosis until death date of any cause or last follow up date, assessed up to 5 years
Event-free survival (EFS) for stratum 2 and stratum 3
Time Frame: Follow up date, assessed up to 5 years
For stratum 2 and stratum 3, Kaplan Meier estimates will be provided for EFS distribution.
Follow up date, assessed up to 5 years
Incidence of adverse events
Time Frame: Up to 5 years
Graded per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Grade 3 and higher toxicities observed by cycle will be listed for each stratum separately. The grade 3 and higher toxicities observed by cycle and by system organ class for the eligible patients will also be listed for each stratum separately. Toxicity data will be reported separately for the radiation therapy phase versus the maintenance therapy phase for clarity of attribution. Toxicity monitoring will include toxicities such as grade 2 or higher pyrexia, uveitis, retinal vein occlusion, retinal pigment epithelial detachment, and decreased left ventricular ejection fraction.
Up to 5 years

Collaborators and Investigators

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

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Rishi R Lulla, Children's Oncology Group

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

February 20, 2020

Primary Completion (Estimated)

September 30, 2027

Study Completion (Estimated)

September 30, 2027

Study Registration Dates

First Submitted

April 17, 2019

First Submitted That Met QC Criteria

April 17, 2019

First Posted (Actual)

April 18, 2019

Study Record Updates

Last Update Posted (Estimated)

April 25, 2024

Last Update Submitted That Met QC Criteria

April 24, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2019-02289 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • ACNS1723 (Other Identifier: CTEP)
  • U10CA180886 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

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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