Ulixertinib in Treating Patients With Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial)
NCT ID: NCT03698994
Last Updated: 2025-12-03
Study Results
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View full resultsBasic Information
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ACTIVE_NOT_RECRUITING
PHASE2
20 participants
INTERVENTIONAL
2018-11-14
2026-03-30
Brief Summary
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Detailed Description
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I. To determine the objective response rate (ORR; complete response + partial response) in pediatric patients treated with BVD-523FB (ulixertinib) with advanced solid tumors (including central nervous system \[CNS\] tumors), non-Hodgkin lymphomas or histiocytic disorders that harbor activating genetic alterations in the MAPK pathway.
SECONDARY OBJECTIVES:
I. To estimate the progression free survival in pediatric patients treated with BVD-523FB (ulixertinib) with advanced solid tumors (including CNS tumors), non-Hodgkin lymphomas or histiocytic disorders that harbor activating genetic alterations in the MAPK pathway.
II. To obtain information about the tolerability of BVD-523FB (ulixertinib) in children and adolescents with relapsed or refractory cancer.
III. To provide preliminary estimates of the pharmacokinetics of BVD-523FB (ulixertinib) in children and adolescents with relapsed or refractory cancer.
EXPLORATORY OBJECTIVES:
I. To evaluate other biomarkers as predictors of response to BVD-523FB (ulixertinib) and specifically, whether tumors that harbor different mutations or fusions will demonstrate differential response to BVD-523FB (ulixertinib) treatment.
II. To explore approaches to profiling changes in tumor genomics over time through evaluation of circulating tumor deoxyribonucleic acid (DNA).
OUTLINE: This is a dose-escalation study.
Patients receive ulixertinib orally (PO) twice daily (BID). Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up periodically.
Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Treatment (ulixertinib)
Patients receive ulixertinib PO BID. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
Pharmacokinetic Study
Ancillary studies
Ulixertinib
Given PO
Interventions
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Pharmacokinetic Study
Ancillary studies
Ulixertinib
Given PO
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Patients must have a body surface area \>= 0.54 m\^2 at the time of study enrollment.
* Patients must have radiographically measurable disease at the time of study enrollment. Patients with neuroblastoma who do not have measurable disease but have metaiodobenzylguanidine (MIBG)+ evaluable disease are eligible. Measurable disease in patients with central nervous system (CNS) involvement is defined as tumor that is measurable in two perpendicular diameters on magnetic resonance imaging (MRI) and visible on more than one slice.
* Note: The following do not qualify as measurable disease:
* Malignant fluid collections (e.g., ascites, pleural effusions)
* Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
* Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography \[PET\] scans) except as noted for neuroblastoma
* Elevated tumor markers in plasma or cerebrospinal fluid (CSF)
* Previously radiated lesions that have not demonstrated clear progression post radiation
* Leptomeningeal lesions that do not meet the measurement requirements for Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
* Karnofsky \>= 50% for patients \> 16 years of age and Lansky \>= 50 for patients =\< 16 years of age. Note: Neurologic deficits in patients with CNS tumors must have been relatively stable for at least 7 days prior to study enrollment. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
* Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately.
* Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive.
* \>= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea).
* Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or ANC counts): \>= 7 days after the last dose of agent.
* Antibodies: \>= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =\< 1.
* Corticosteroids: If used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid.
* Hematopoietic growth factors: \>= 14 days after the last dose of a long-acting growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor. For growth factors that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair and the study-assigned research coordinator.
* Interleukins, Interferons and Cytokines (other than hematopoietic growth factors): \>= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors).
* Stem cell Infusions (with or without total body irradiation \[TBI\]):
* Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including DLI or boost infusion: \>= 84 days after infusion and no evidence of graft versus host disease (GVHD).
* Autologous stem cell infusion including boost infusion: \>= 42 days.
* Cellular Therapy: \>= 42 days after the completion of any type of cellular therapy (e.g. modified T cells, natural killer \[NK\] cells, dendritic cells, etc.).
* Radiotherapy (XRT)/External Beam Irradiation including Protons: \>= 14 days after local XRT; \>= 150 days after TBI, craniospinal XRT or if radiation to \>= 50% of the pelvis; \>= 42 days if other substantial brain metastases (BM) radiation.
* Note: Radiation may not be delivered to "measurable disease" tumor site(s) being used to follow response to subprotocol treatment.
* Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): \>= 42 days after systemically administered radiopharmaceutical therapy.
* Patients must not have received prior exposure to BVD-523FB (ulixertinib) or other ERK inhibitors.
* For patients with solid tumors without known bone marrow involvement: Peripheral absolute neutrophil count (ANC) \>= 1000/mm\^3 (within 7 days prior to enrollment).
* For patients with solid tumors without known bone marrow involvement: Platelet count \>= 100,000/mm\^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).
* Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity.
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 ml/min/1.73 m\^2, or (within 7 days prior to enrollment).
* A serum creatinine based on age/gender (within 7 days prior to enrollment).
* Age 1 to \< 2 years, maximum serum creatinine (mg/dL) male 0.6, female 0.6
* Age 2 to \< 6 years, maximum serum creatinine (mg/dL) male 0.8, female 0.8
* Age 6 to \< 10 years, maximum serum creatinine (mg/dL) male 1, female 1
* Age 10 to \< 13 years, maximum serum creatinine (mg/dL) male 1.2, female 1.2
* Age 13 to \< 16 years, maximum serum creatinine (mg/dL) male 1.5, female 1.4
* Age \>= 16 years, maximum serum creatinine (mg/dL) male 1.7, female 1.4
* Bilirubin (sum of conjugated + unconjugated) =\< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment).
* Serum glutamate-pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L. (For the purpose of this study, the ULN for SGPT is 45 U/L.) (within 7 days prior to enrollment).
* Serum albumin \>= 2 g/dL (within 7 days prior to enrollment).
* Shortening fraction of \>= 27% by echocardiogram, or (within 7 days prior to enrollment).
* Ejection fraction of \>= 50% by gated radionuclide study (within 7 days prior to enrollment).
* QTc interval =\< 480 milliseconds (within 7 days prior to enrollment).
* Patients must be able to swallow intact capsules.
* All patients and/or their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.
Exclusion Criteria
* Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible. If used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid.
* Patients who are currently receiving another investigational drug are not eligible.
* Patients who are currently receiving other anti-cancer agents are not eligible.
* Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial.
* Patients who are currently receiving drugs that are strong inducers or inhibitors of CYP3A4 are not eligible. Strong inducers or inhibitors of CYP3A4 should be avoided from 14 days prior to enrollment to the end of the study. Note: CYP3A4 inducing anti-epileptic drugs and dexamethasone for CNS tumors or metastases, on a stable dose, are allowed.
* Patients who are currently receiving drugs that are strong inducers or inhibitors of CYP1A2 and CYP2D6 are not eligible. Strong inhibitors of CYP1A2 (e.g., ciprofloxacin, enoxacin, fluvoxamine, zafirlukast) should be avoided from 14 days prior to enrollment to the end of the study. Strong inhibitors of CYP2D6 (e.g., bupropion, paroxetine, fluoxetine, quinidine, terbinafine) should also be avoided from 14 days prior to enrollment to the end of the study.
* Patients with known significant ophthalmologic conditions (uncontrolled glaucoma, history of retinal vein occlusion or retinal detachment, excluding patients with longstanding findings secondary to existing conditions) are not eligible.
* Patients who have an uncontrolled infection are not eligible.
* Patients who have received a prior solid organ transplantation are not eligible.
* Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.
12 Months
21 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
Responsible Party
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Principal Investigators
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Kieuhoa T Vo
Role: PRINCIPAL_INVESTIGATOR
Children's Oncology Group
Locations
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Children's Hospital of Alabama
Birmingham, Alabama, United States
Providence Alaska Medical Center
Anchorage, Alaska, United States
Banner Children's at Desert
Mesa, Arizona, United States
Banner University Medical Center - Tucson
Tucson, Arizona, United States
Arkansas Children's Hospital
Little Rock, Arkansas, United States
Kaiser Permanente Downey Medical Center
Downey, California, United States
Loma Linda University Medical Center
Loma Linda, California, United States
Miller Children's and Women's Hospital Long Beach
Long Beach, California, United States
Children's Hospital Los Angeles
Los Angeles, California, United States
Mattel Children's Hospital UCLA
Los Angeles, California, United States
Valley Children's Hospital
Madera, California, United States
UCSF Benioff Children's Hospital Oakland
Oakland, California, United States
Kaiser Permanente-Oakland
Oakland, California, United States
UCSF Medical Center-Mission Bay
San Francisco, California, United States
Children's Hospital Colorado
Aurora, Colorado, United States
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
Denver, Colorado, United States
Alfred I duPont Hospital for Children
Wilmington, Delaware, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
UF Health Cancer Institute - Gainesville
Gainesville, Florida, United States
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, United States
Nicklaus Children's Hospital
Miami, Florida, United States
AdventHealth Orlando
Orlando, Florida, United States
Arnold Palmer Hospital for Children
Orlando, Florida, United States
Nemours Children's Hospital
Orlando, Florida, United States
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, United States
Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa, Florida, United States
Saint Mary's Medical Center
West Palm Beach, Florida, United States
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta, Georgia, United States
Memorial Health University Medical Center
Savannah, Georgia, United States
Saint Luke's Cancer Institute - Boise
Boise, Idaho, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States
Saint Jude Midwest Affiliate
Peoria, Illinois, United States
Southern Illinois University School of Medicine
Springfield, Illinois, United States
Riley Hospital for Children
Indianapolis, Indiana, United States
Ascension Saint Vincent Indianapolis Hospital
Indianapolis, Indiana, United States
Blank Children's Hospital
Des Moines, Iowa, United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, United States
Children's Hospital New Orleans
New Orleans, Louisiana, United States
Ochsner Medical Center Jefferson
New Orleans, Louisiana, United States
Eastern Maine Medical Center
Bangor, Maine, United States
Sinai Hospital of Baltimore
Baltimore, Maryland, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
C S Mott Children's Hospital
Ann Arbor, Michigan, United States
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
Grand Rapids, Michigan, United States
Bronson Methodist Hospital
Kalamazoo, Michigan, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, United States
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, United States
University of Mississippi Medical Center
Jackson, Mississippi, United States
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, United States
Cardinal Glennon Children's Medical Center
St Louis, Missouri, United States
Washington University School of Medicine
St Louis, Missouri, United States
Mercy Hospital Saint Louis
St Louis, Missouri, United States
Children's Hospital and Medical Center of Omaha
Omaha, Nebraska, United States
University of Nebraska Medical Center
Omaha, Nebraska, United States
Hackensack University Medical Center
Hackensack, New Jersey, United States
Morristown Medical Center
Morristown, New Jersey, United States
Saint Peter's University Hospital
New Brunswick, New Jersey, United States
Albany Medical Center
Albany, New York, United States
Roswell Park Cancer Institute
Buffalo, New York, United States
The Steven and Alexandra Cohen Children's Medical Center of New York
New Hyde Park, New York, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
NYP/Weill Cornell Medical Center
New York, New York, United States
University of Rochester
Rochester, New York, United States
State University of New York Upstate Medical University
Syracuse, New York, United States
Mission Hospital
Asheville, North Carolina, United States
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, United States
Duke University Medical Center
Durham, North Carolina, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
Nationwide Children's Hospital
Columbus, Ohio, United States
Dayton Children's Hospital
Dayton, Ohio, United States
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
Toledo, Ohio, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States
Legacy Emanuel Children's Hospital
Portland, Oregon, United States
Oregon Health and Science University
Portland, Oregon, United States
Geisinger Medical Center
Danville, Pennsylvania, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, United States
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, United States
East Tennessee Childrens Hospital
Knoxville, Tennessee, United States
Saint Jude Children's Research Hospital
Memphis, Tennessee, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, United States
Dell Children's Medical Center of Central Texas
Austin, Texas, United States
Medical City Dallas Hospital
Dallas, Texas, United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, United States
Cook Children's Medical Center
Fort Worth, Texas, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, United States
M D Anderson Cancer Center
Houston, Texas, United States
Children's Hospital of San Antonio
San Antonio, Texas, United States
Methodist Children's Hospital of South Texas
San Antonio, Texas, United States
Scott and White Memorial Hospital
Temple, Texas, United States
Primary Children's Hospital
Salt Lake City, Utah, United States
University of Vermont and State Agricultural College
Burlington, Vermont, United States
Children's Hospital of The King's Daughters
Norfolk, Virginia, United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, United States
Seattle Children's Hospital
Seattle, Washington, United States
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington, United States
Madigan Army Medical Center
Tacoma, Washington, United States
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, United States
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, United States
San Jorge Children's Hospital
San Juan, , Puerto Rico
University Pediatric Hospital
San Juan, , Puerto Rico
Countries
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References
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Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14.
Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan
Other Identifiers
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NCI-2018-02150
Identifier Type: REGISTRY
Identifier Source: secondary_id
APEC1621J
Identifier Type: OTHER
Identifier Source: secondary_id
APEC1621J
Identifier Type: OTHER
Identifier Source: secondary_id
NCI-2018-02150
Identifier Type: -
Identifier Source: org_study_id
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