Ulixertinib in Treating Patients With Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial)
NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice) - Phase 2 Subprotocol of BVD-523FB (Ulixertinib) in Patients With Tumors Harboring Activating MAPK Pathway Mutations
3 other identifiers
interventional
20
2 countries
107
Brief Summary
This phase II Pediatric MATCH trial studies how well ulixertinib works in treating patients with solid tumors that have spread to other places in the body (advanced), non-Hodgkin lymphoma, or histiocytic disorders that have a genetic alteration (mutation) in a signaling pathway called MAPK. A signaling pathway consists of a group of molecules in a cell that control one or more cell functions. Genes in the MAPK pathway are frequently mutated in many types of cancers. Ulixertinib may stop the growth of cancer cells that have mutations in the MAPK pathway.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Nov 2018
Longer than P75 for phase_2
107 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 5, 2018
CompletedFirst Posted
Study publicly available on registry
October 9, 2018
CompletedStudy Start
First participant enrolled
November 14, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 31, 2022
CompletedResults Posted
Study results publicly available
May 16, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
March 30, 2027
ExpectedApril 23, 2026
March 1, 2026
3.4 years
October 5, 2018
April 20, 2023
April 7, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Objective Response Rate (ORR = Complete Response [CR] + Partial Response [PR]) in Pediatric Patients Treated With BVD-523FB (Ulixertinib)
ORR will be defined as complete response + partial response and assessed by Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Response rates will be calculated as the percent of evaluable patients who are responders, and confidence intervals will be constructed using the Wilson score interval method.
From enrollment to the end of treatment, up to 2 years
Secondary Outcomes (3)
Progression Free Survival (PFS) in Pediatric Patients Treated With Ulixertinib
From initiation of treatment to disease progression, disease recurrence, or death from any cause assessed up to 2 years
Percentage of Patients Experiencing Grade 3 or 4 Adverse Events
From enrollment to the end of treatment, up to 2 years
Preliminary Estimates of the Pharmacokinetics of Ulixertinib in Children and Adolescents With Relapsed or Refractory Cancer
Pre-dose and 1, 2, 4, and 6-8 hours after dose on cycle 1, day 1; and pre-dose on cycle 1, day 2, and cycle 1, day 15
Other Outcomes (2)
Other Biomarkers as Predictors of Response to Ulixertinib and Whether Tumors That Harbor Different Mutations or Fusions Will Demonstrate Differential Response to Treatment
Up to 2 years
Profiling Changes in Tumor Genomics Over Time Through Evaluation of Circulating Tumor Deoxyribonucleic Acid (DNA)
Up to 2 years
Study Arms (1)
Treatment (ulixertinib)
EXPERIMENTALPatients receive ulixertinib PO BID. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
Interventions
Ancillary studies
Eligibility Criteria
You may qualify if:
- Patient must have enrolled onto APEC1621SC and must have been given a treatment assignment to MATCH to APEC1621J based on the presence of an actionable mutation.
- 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.
- +31 more criteria
You may not qualify if:
- Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method for the duration of study treatment and for 3 months after last dose of BVD-523FB (ulixertinib).
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (107)
Children's Hospital of Alabama
Birmingham, Alabama, 35233, United States
Providence Alaska Medical Center
Anchorage, Alaska, 99508, United States
Banner Children's at Desert
Mesa, Arizona, 85202, United States
Banner University Medical Center - Tucson
Tucson, Arizona, 85719, United States
Arkansas Children's Hospital
Little Rock, Arkansas, 72202-3591, United States
Kaiser Permanente Downey Medical Center
Downey, California, 90242, United States
Loma Linda University Medical Center
Loma Linda, California, 92354, United States
Miller Children's and Women's Hospital Long Beach
Long Beach, California, 90806, United States
Children's Hospital Los Angeles
Los Angeles, California, 90027, United States
Mattel Children's Hospital UCLA
Los Angeles, California, 90095, United States
Valley Children's Hospital
Madera, California, 93636, United States
UCSF Benioff Children's Hospital Oakland
Oakland, California, 94609, United States
Kaiser Permanente-Oakland
Oakland, California, 94611, United States
UCSF Medical Center-Mission Bay
San Francisco, California, 94158, United States
Children's Hospital Colorado
Aurora, Colorado, 80045, United States
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
Denver, Colorado, 80218, United States
Alfred I duPont Hospital for Children
Wilmington, Delaware, 19803, United States
Children's National Medical Center
Washington D.C., District of Columbia, 20010, United States
UF Health Cancer Institute - Gainesville
Gainesville, Florida, 32610, United States
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, 32207, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136, United States
Nicklaus Children's Hospital
Miami, Florida, 33155, United States
AdventHealth Orlando
Orlando, Florida, 32803, United States
Arnold Palmer Hospital for Children
Orlando, Florida, 32806, United States
Nemours Children's Hospital
Orlando, Florida, 32827, United States
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, 33701, United States
Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa, Florida, 33607, United States
Saint Mary's Medical Center
West Palm Beach, Florida, 33407, United States
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta, Georgia, 30329, United States
Memorial Health University Medical Center
Savannah, Georgia, 31404, United States
Saint Luke's Cancer Institute - Boise
Boise, Idaho, 83712, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637, United States
Saint Jude Midwest Affiliate
Peoria, Illinois, 61637, United States
Southern Illinois University School of Medicine
Springfield, Illinois, 62702, United States
Riley Hospital for Children
Indianapolis, Indiana, 46202, United States
Ascension Saint Vincent Indianapolis Hospital
Indianapolis, Indiana, 46260, United States
Blank Children's Hospital
Des Moines, Iowa, 50309, United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242, United States
Children's Hospital New Orleans
New Orleans, Louisiana, 70118, United States
Ochsner Medical Center Jefferson
New Orleans, Louisiana, 70121, United States
Eastern Maine Medical Center
Bangor, Maine, 04401, United States
Sinai Hospital of Baltimore
Baltimore, Maryland, 21215, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287, United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109, United States
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
Grand Rapids, Michigan, 49503, United States
Bronson Methodist Hospital
Kalamazoo, Michigan, 49007, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, 55404, United States
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, 55455, United States
University of Mississippi Medical Center
Jackson, Mississippi, 39216, United States
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108, United States
Cardinal Glennon Children's Medical Center
St Louis, Missouri, 63104, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Mercy Hospital Saint Louis
St Louis, Missouri, 63141, United States
Children's Hospital and Medical Center of Omaha
Omaha, Nebraska, 68114, United States
University of Nebraska Medical Center
Omaha, Nebraska, 68198, United States
Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
Morristown Medical Center
Morristown, New Jersey, 07960, United States
Saint Peter's University Hospital
New Brunswick, New Jersey, 08901, United States
Albany Medical Center
Albany, New York, 12208, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
The Steven and Alexandra Cohen Children's Medical Center of New York
New Hyde Park, New York, 11040, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
NYP/Weill Cornell Medical Center
New York, New York, 10065, United States
University of Rochester
Rochester, New York, 14642, United States
State University of New York Upstate Medical University
Syracuse, New York, 13210, United States
Mission Hospital
Asheville, North Carolina, 28801, United States
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, 28203, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229, United States
Nationwide Children's Hospital
Columbus, Ohio, 43205, United States
Dayton Children's Hospital
Dayton, Ohio, 45404, United States
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
Toledo, Ohio, 43606, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Legacy Emanuel Children's Hospital
Portland, Oregon, 97227, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
Geisinger Medical Center
Danville, Pennsylvania, 17822, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224, United States
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, 29605, United States
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, 57117-5134, United States
East Tennessee Childrens Hospital
Knoxville, Tennessee, 37916, United States
Saint Jude Children's Research Hospital
Memphis, Tennessee, 38105, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232, United States
Dell Children's Medical Center of Central Texas
Austin, Texas, 78723, United States
Medical City Dallas Hospital
Dallas, Texas, 75230, United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390, United States
Cook Children's Medical Center
Fort Worth, Texas, 76104, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030, United States
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Children's Hospital of San Antonio
San Antonio, Texas, 78207, United States
Methodist Children's Hospital of South Texas
San Antonio, Texas, 78229, United States
Scott and White Memorial Hospital
Temple, Texas, 76508, United States
Primary Children's Hospital
Salt Lake City, Utah, 84113, United States
University of Vermont and State Agricultural College
Burlington, Vermont, 05405, United States
Children's Hospital of The King's Daughters
Norfolk, Virginia, 23507, United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298, United States
Seattle Children's Hospital
Seattle, Washington, 98105, United States
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington, 99204, United States
Madigan Army Medical Center
Tacoma, Washington, 98431, United States
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792, United States
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226, United States
San Jorge Children's Hospital
San Juan, 00912, Puerto Rico
University Pediatric Hospital
San Juan, 00926, Puerto Rico
Related Publications (1)
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.
PMID: 31401903DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Results Reporting Coordinator
- Organization
- Children's Oncology Group
Study Officials
- PRINCIPAL INVESTIGATOR
Kieuhoa T Vo
Children's Oncology Group
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 5, 2018
First Posted
October 9, 2018
Study Start
November 14, 2018
Primary Completion
March 31, 2022
Study Completion (Estimated)
March 30, 2027
Last Updated
April 23, 2026
Results First Posted
May 16, 2023
Record last verified: 2026-03