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AzTrials

Anaplastic AstrocytomaPhase 2NCT03919071

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

A Phase 2 study testing Biospecimen Collection, Dabrafenib Mesylate and Lumbar Puncture in people with Anaplastic Astrocytoma and Anaplastic Astrocytoma, Not Otherwise Specified, run by National Cancer Institute (NCI) at 131 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 3 to 25 years
What is being tested?
Biospecimen Collection, Dabrafenib Mesylate and Lumbar Puncture
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
58 participants
Where
131 sitesin 2 countries
Study dates
20 Feb 2020to 30 Sep 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 3 to 25 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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.
Show all 30Show fewer
  • 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/sex 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)
  • The threshold creatinine values in this table were derived from the Schwartz formula for estimating GFR utilizing child length and stature data published by the Centers for Disease Control and Prevention (CDC).
  • 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.
  • 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.
  • All patients and/or their parents or legal guardians must sign a written informed consent.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

131 sites in 2 countries.

131 sites in 2 countries

United States130 sites

  • Children's Hospital Medical Center of Akron

    Akron, Ohio, 44308

  • Albany Medical Center

    Albany, New York, 12208

  • University of New Mexico Cancer Center

    Albuquerque, New Mexico, 87106

  • Lehigh Valley Hospital-Cedar Crest

    Allentown, Pennsylvania, 18103

  • C S Mott Children's Hospital

    Ann Arbor, Michigan, 48109

  • Mission Hospital

    Asheville, North Carolina, 28801

  • Children's Healthcare of Atlanta - Arthur M Blank Hospital

    Atlanta, Georgia, 30329

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

  • Dell Children's Medical Center of Central Texas

    Austin, Texas, 78723

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • Eastern Maine Medical Center

    Bangor, Maine, 04401

  • Walter Reed National Military Medical Center

    Bethesda, Maryland, 20889-5600

  • Children's Hospital of Alabama

    Birmingham, Alabama, 35233

  • Saint Luke's Cancer Institute - Boise

    Boise, Idaho, 83712

  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts, 02114

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Carolinas Medical Center/Levine Cancer Institute

    Charlotte, North Carolina, 28203

  • Novant Health Presbyterian Medical Center

    Charlotte, North Carolina, 28204

  • University of Virginia Cancer Center

    Charlottesville, Virginia, 22908

  • Lurie Children's Hospital-Chicago

    Chicago, Illinois, 60611

  • University of Illinois

    Chicago, Illinois, 60612

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • Rainbow Babies and Childrens Hospital

    Cleveland, Ohio, 44106

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Prisma Health Richland Hospital

    Columbia, South Carolina, 29203

  • Nationwide Children's Hospital

    Columbus, Ohio, 43205

  • Medical City Dallas Hospital

    Dallas, Texas, 75230

  • UT Southwestern/Simmons Cancer Center-Dallas

    Dallas, Texas, 75390

  • Dayton Children's Hospital

    Dayton, Ohio, 45404

  • Children's Hospital of Michigan

    Detroit, Michigan, 48201

  • Kaiser Permanente Downey Medical Center

    Downey, California, 90242

  • Sanford Broadway Medical Center

    Fargo, North Dakota, 58122

  • Golisano Children's Hospital of Southwest Florida

    Fort Myers, Florida, 33908

  • Cook Children's Medical Center

    Fort Worth, Texas, 76104

  • UF Health Cancer Institute - Gainesville

    Gainesville, Florida, 32610

  • Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital

    Grand Rapids, Michigan, 49503

  • East Carolina University

    Greenville, North Carolina, 27834

  • BI-LO Charities Children's Cancer Center

    Greenville, South Carolina, 29605

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Connecticut Children's Medical Center

    Hartford, Connecticut, 06106

  • Penn State Children's Hospital

    Hershey, Pennsylvania, 17033

  • Memorial Regional Hospital/Joe DiMaggio Children's Hospital

    Hollywood, Florida, 33021

  • Kapiolani Medical Center for Women and Children

    Honolulu, Hawaii, 96826

  • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

    Houston, Texas, 77030

  • Riley Hospital for Children

    Indianapolis, Indiana, 46202

  • Ascension Saint Vincent Indianapolis Hospital

    Indianapolis, Indiana, 46260

  • University of Iowa/Holden Comprehensive Cancer Center

    Iowa City, Iowa, 52242

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • Nemours Children's Clinic-Jacksonville

    Jacksonville, Florida, 32207

  • Bronson Methodist Hospital

    Kalamazoo, Michigan, 49007

  • Children's Mercy Hospitals and Clinics

    Kansas City, Missouri, 64108

  • East Tennessee Childrens Hospital

    Knoxville, Tennessee, 37916

  • University of Kentucky/Markey Cancer Center

    Lexington, Kentucky, 40536

  • Arkansas Children's Hospital

    Little Rock, Arkansas, 72202-3591

  • Loma Linda University Medical Center

    Loma Linda, California, 92354

  • Miller Children's and Women's Hospital Long Beach

    Long Beach, California, 90806

  • Children's Hospital Los Angeles

    Los Angeles, California, 90027

  • Cedars-Sinai Medical Center

    Los Angeles, California, 90048

  • Norton Children's Hospital

    Louisville, Kentucky, 40202

  • University of Wisconsin Carbone Cancer Center - University Hospital

    Madison, Wisconsin, 53792

  • Marshfield Medical Center-Marshfield

    Marshfield, Wisconsin, 54449

  • Saint Jude Children's Research Hospital

    Memphis, Tennessee, 38105

  • Banner Children's at Desert

    Mesa, Arizona, 85202

  • University of Miami Miller School of Medicine-Sylvester Cancer Center

    Miami, Florida, 33136

  • Nicklaus Children's Hospital

    Miami, Florida, 33155

  • Children's Hospital of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Children's Hospitals and Clinics of Minnesota - Minneapolis

    Minneapolis, Minnesota, 55404

  • Morristown Medical Center

    Morristown, New Jersey, 07960

  • The Children's Hospital at TriStar Centennial

    Nashville, Tennessee, 37203

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital

    New Brunswick, New Jersey, 08903

  • Yale University

    New Haven, Connecticut, 06520

  • The Steven and Alexandra Cohen Children's Medical Center of New York

    New Hyde Park, New York, 11040

  • Children's Hospital New Orleans

    New Orleans, Louisiana, 70118

  • Ochsner Medical Center Jefferson

    New Orleans, Louisiana, 70121

  • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

    New York, New York, 10032

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Newark Beth Israel Medical Center

    Newark, New Jersey, 07112

  • Children's Hospital of The King's Daughters

    Norfolk, Virginia, 23507

  • Kaiser Permanente-Oakland

    Oakland, California, 94611

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • Children's Hospital and Medical Center of Omaha

    Omaha, Nebraska, 68114

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

  • Children's Hospital of Orange County

    Orange, California, 92868

  • AdventHealth Orlando

    Orlando, Florida, 32803

  • Arnold Palmer Hospital for Children

    Orlando, Florida, 32806

  • Nemours Children's Hospital

    Orlando, Florida, 32827

  • Lucile Packard Children's Hospital Stanford University

    Palo Alto, California, 94304

  • Saint Joseph's Regional Medical Center

    Paterson, New Jersey, 07503

  • Sacred Heart Hospital

    Pensacola, Florida, 32504

  • OSF Children's Hospital of Illinois

    Peoria, Illinois, 61637

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Phoenix Childrens Hospital

    Phoenix, Arizona, 85016

  • Children's Hospital of Pittsburgh of UPMC

    Pittsburgh, Pennsylvania, 15224

  • Legacy Emanuel Children's Hospital

    Portland, Oregon, 97227

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • Rhode Island Hospital

    Providence, Rhode Island, 02903

  • VCU Massey Comprehensive Cancer Center

    Richmond, Virginia, 23298

  • Carilion Children's

    Roanoke, Virginia, 24014

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

  • Corewell Health Children's

    Royal Oak, Michigan, 48073

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California, 95817

  • Primary Children's Hospital

    Salt Lake City, Utah, 84113

  • Children's Hospital of San Antonio

    San Antonio, Texas, 78207

  • University of Texas Health Science Center at San Antonio

    San Antonio, Texas, 78229

  • UCSF Medical Center-Mission Bay

    San Francisco, California, 94158

  • Memorial Health University Medical Center

    Savannah, Georgia, 31404

  • Seattle Children's Hospital

    Seattle, Washington, 98105

  • Providence Sacred Heart Medical Center and Children's Hospital

    Spokane, Washington, 99204

  • Cardinal Glennon Children's Medical Center

    St Louis, Missouri, 63104

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Mercy Hospital Saint Louis

    St Louis, Missouri, 63141

  • Johns Hopkins All Children's Hospital

    St. Petersburg, Florida, 33701

  • State University of New York Upstate Medical University

    Syracuse, New York, 13210

  • Mary Bridge Children's Hospital and Health Center

    Tacoma, Washington, 98405

  • Tampa General Hospital

    Tampa, Florida, 33606

  • Saint Joseph's Hospital/Children's Hospital-Tampa

    Tampa, Florida, 33607

  • Scott and White Memorial Hospital

    Temple, Texas, 76508

  • Montefiore Medical Center - Moses Campus

    The Bronx, New York, 10467

  • ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital

    Toledo, Ohio, 43606

  • Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

    Torrance, California, 90502

  • MedStar Georgetown University Hospital

    Washington D.C., District of Columbia, 20007

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010

  • Saint Mary's Medical Center

    West Palm Beach, Florida, 33407

  • Alfred I duPont Hospital for Children

    Wilmington, Delaware, 19803

  • Wake Forest University Health Sciences

    Winston-Salem, North Carolina, 27157

Other trials in United States

Puerto Rico1 site

  • HIMA San Pablo Oncologic Hospital

    Caguas, 00726

Other trials in Puerto Rico

About this study

Official title: 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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. 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:

  1. 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:

  1. 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.

Being tested
Biospecimen Collection, Dabrafenib Mesylate, Lumbar Puncture, Magnetic Resonance Imaging, Radiation Therapy
Medical subject headings
Astrocytoma, Glioblastoma, Glioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo collection of blood

  • Dabrafenib MesylateDrug

    Also called Dabrafenib Methanesulfonate, GSK2118436 Methane Sulfonate Salt, GSK2118436B, Tafinlar

    Given PO

  • Lumbar PunctureProcedure or surgery

    Also called LP, Spinal Tap

    Undergo lumbar puncture

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • Radiation TherapyRadiation

    Also called Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate

    Undergo RT

  • Trametinib Dimethyl SulfoxideDrug

    Also called Mekinist, Meqsel, Spexotras

    Given PO

Study groups in NCT03919071
Study groupRoleWhat they receive
Treatment (radiation therapy, dabrafenib, trametinib)ExperimentalPatients 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.
Receives: Procedure: Biospecimen Collection; Drug: Dabrafenib Mesylate; Procedure: Lumbar Puncture; Procedure: Magnetic Resonance Imaging; Radiation: Radiation Therapy; Drug: Trametinib Dimethyl Sulfoxide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Event-free survival (EFS) for stratum 1

    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.

    Measured: 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 outcomes (3)

  1. Overall survival (OS) for stratum 1, stratum 2, and stratum 3

    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.

    Measured: From the date of diagnosis until death date of any cause or last follow up date, assessed up to 5 years

  2. Event-free survival (EFS) for stratum 2 and stratum 3

    For stratum 2 and stratum 3, Kaplan Meier estimates will be provided for EFS distribution.

    Measured: Follow up date, assessed up to 5 years

  3. Incidence of adverse events

    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.

    Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Apr 2019
  2. Study start20 Feb 2020
  3. Primary completion30 Sep 2027 (estimated)
  4. Study completion30 Sep 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
58 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03919071
Sponsor's protocol ID
NCI-2019-02289
Other IDs
NCI-2019-02289, ACNS1723, ACNS1723, U10CA180886
Status last verified
Jul 2026
First submitted
17 Apr 2019
Last updated
3 Nov 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Publications

  • Shahid S, Kushner BH, Modak S, Basu EM, Rubin EM, Gundem G, Papaemmanuil E, Roberts SS. Association of BRAF V600E mutations with vasoactive intestinal peptide syndrome in MYCN-amplified neuroblastoma. Pediatr Blood Cancer. 2021 Oct;68(10):e29265. doi: 10.1002/pbc.29265. Epub 2021 Jul 31.

    PubMed 34331515

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Biospecimen Collection, Dabrafenib Mesylate and Lumbar Puncture in people with Anaplastic Astrocytoma and Anaplastic Astrocytoma, Not Otherwise Specified, run by National Cancer Institute (NCI) at 131 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 30 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 3 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 131 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03919071, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Nov 2026.

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