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Ulixertinib in Treating Patients With Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial)

Primary Purpose

Advanced Malignant Solid Neoplasm, Recurrent Ependymal Tumor, Recurrent Ewing Sarcoma

Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Pharmacokinetic Study
Ulixertinib
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Malignant Solid Neoplasm

Eligibility Criteria

12 Months - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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.
    • 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:

  • 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.

Sites / Locations

  • Children's Hospital of Alabama
  • Providence Alaska Medical Center
  • Banner Children's at Desert
  • Banner University Medical Center - Tucson
  • Arkansas Children's Hospital
  • Kaiser Permanente Downey Medical Center
  • Loma Linda University Medical Center
  • Miller Children's and Women's Hospital Long Beach
  • Children's Hospital Los Angeles
  • Mattel Children's Hospital UCLA
  • Valley Children's Hospital
  • UCSF Benioff Children's Hospital Oakland
  • Kaiser Permanente-Oakland
  • UCSF Medical Center-Mission Bay
  • Children's Hospital Colorado
  • Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
  • Alfred I duPont Hospital for Children
  • Children's National Medical Center
  • University of Florida Health Science Center - Gainesville
  • Nemours Children's Clinic-Jacksonville
  • University of Miami Miller School of Medicine-Sylvester Cancer Center
  • Nicklaus Children's Hospital
  • AdventHealth Orlando
  • Arnold Palmer Hospital for Children
  • Nemours Children's Hospital
  • Johns Hopkins All Children's Hospital
  • Saint Joseph's Hospital/Children's Hospital-Tampa
  • Saint Mary's Hospital
  • Children's Healthcare of Atlanta - Egleston
  • Memorial Health University Medical Center
  • Saint Luke's Cancer Institute - Boise
  • University of Chicago Comprehensive Cancer Center
  • Saint Jude Midwest Affiliate
  • Southern Illinois University School of Medicine
  • Riley Hospital for Children
  • Ascension Saint Vincent Indianapolis Hospital
  • Blank Children's Hospital
  • University of Iowa/Holden Comprehensive Cancer Center
  • Children's Hospital New Orleans
  • Ochsner Medical Center Jefferson
  • Eastern Maine Medical Center
  • Sinai Hospital of Baltimore
  • Johns Hopkins University/Sidney Kimmel Cancer Center
  • Massachusetts General Hospital Cancer Center
  • Dana-Farber Cancer Institute
  • C S Mott Children's Hospital
  • Helen DeVos Children's Hospital at Spectrum Health
  • Bronson Methodist Hospital
  • Children's Hospitals and Clinics of Minnesota - Minneapolis
  • University of Minnesota/Masonic Cancer Center
  • Mayo Clinic in Rochester
  • University of Mississippi Medical Center
  • Children's Mercy Hospitals and Clinics
  • Cardinal Glennon Children's Medical Center
  • Washington University School of Medicine
  • Mercy Hospital Saint Louis
  • Children's Hospital and Medical Center of Omaha
  • University of Nebraska Medical Center
  • Hackensack University Medical Center
  • Morristown Medical Center
  • Saint Peter's University Hospital
  • Albany Medical Center
  • Roswell Park Cancer Institute
  • The Steven and Alexandra Cohen Children's Medical Center of New York
  • Laura and Isaac Perlmutter Cancer Center at NYU Langone
  • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
  • Memorial Sloan Kettering Cancer Center
  • NYP/Weill Cornell Medical Center
  • University of Rochester
  • State University of New York Upstate Medical University
  • Mission Hospital
  • Carolinas Medical Center/Levine Cancer Institute
  • Duke University Medical Center
  • Cincinnati Children's Hospital Medical Center
  • Nationwide Children's Hospital
  • Dayton Children's Hospital
  • ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
  • University of Oklahoma Health Sciences Center
  • Legacy Emanuel Children's Hospital
  • Oregon Health and Science University
  • Geisinger Medical Center
  • Children's Hospital of Philadelphia
  • Children's Hospital of Pittsburgh of UPMC
  • BI-LO Charities Children's Cancer Center
  • Sanford USD Medical Center - Sioux Falls
  • East Tennessee Childrens Hospital
  • Saint Jude Children's Research Hospital
  • Vanderbilt University/Ingram Cancer Center
  • Dell Children's Medical Center of Central Texas
  • Medical City Dallas Hospital
  • UT Southwestern/Simmons Cancer Center-Dallas
  • Cook Children's Medical Center
  • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
  • M D Anderson Cancer Center
  • Children's Hospital of San Antonio
  • Methodist Children's Hospital of South Texas
  • University of Texas Health Science Center at San Antonio
  • Scott and White Memorial Hospital
  • Primary Children's Hospital
  • University of Vermont and State Agricultural College
  • Children's Hospital of The King's Daughters
  • Virginia Commonwealth University/Massey Cancer Center
  • Seattle Children's Hospital
  • Providence Sacred Heart Medical Center and Children's Hospital
  • Madigan Army Medical Center
  • University of Wisconsin Carbone Cancer Center
  • Children's Hospital of Wisconsin
  • San Jorge Children's Hospital
  • University Pediatric Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (ulixertinib)

Arm Description

Patients receive ulixertinib PO BID. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Progression Free Survival (PFS) in Pediatric Patients Treated With Ulixertinib
PFS along with the confidence intervals will be estimated using the Kaplan-Meier method.
Percentage of Patients Experiencing Grade 3 or 4 Adverse Events
Will be graded according to Common Terminology Criteria for Adverse Events version 5.0. Any eligible patient who receives at least one dose of protocol therapy will be considered in the evaluation of toxicity.
Preliminary Estimates of the Pharmacokinetics of Ulixertinib in Children and Adolescents With Relapsed or Refractory Cancer
Will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).

Full Information

First Posted
October 5, 2018
Last Updated
May 18, 2023
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT03698994
Brief Title
Ulixertinib in Treating Patients With Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial)
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 1, 2018 (Actual)
Primary Completion Date
March 31, 2022 (Actual)
Study Completion Date
April 7, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
PRIMARY OBJECTIVES: 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Malignant Solid Neoplasm, Recurrent Ependymal Tumor, Recurrent Ewing Sarcoma, Recurrent Glioma, Recurrent Hepatoblastoma, Recurrent Histiocytic and Dendritic Cell Neoplasm, Recurrent Langerhans Cell Histiocytosis, Recurrent Malignant Germ Cell Tumor, Recurrent Malignant Solid Neoplasm, Recurrent Medulloblastoma, Recurrent Neuroblastoma, Recurrent Non-Hodgkin Lymphoma, Recurrent Osteosarcoma, Recurrent Peripheral Primitive Neuroectodermal Tumor, Recurrent Primary Malignant Central Nervous System Neoplasm, Recurrent Rhabdoid Tumor, Recurrent Rhabdomyosarcoma, Recurrent Soft Tissue Sarcoma, Refractory Ependymoma, Refractory Ewing Sarcoma, Refractory Glioma, Refractory Hepatoblastoma, Refractory Histiocytic and Dendritic Cell Neoplasm, Refractory Langerhans Cell Histiocytosis, Refractory Malignant Germ Cell Tumor, Refractory Malignant Solid Neoplasm, Refractory Medulloblastoma, Refractory Neuroblastoma, Refractory Non-Hodgkin Lymphoma, Refractory Osteosarcoma, Refractory Peripheral Primitive Neuroectodermal Tumor, Refractory Primary Malignant Central Nervous System Neoplasm, Refractory Rhabdoid Tumor, Refractory Rhabdomyosarcoma, Refractory Soft Tissue Sarcoma, Wilms Tumor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (ulixertinib)
Arm Type
Experimental
Arm Description
Patients receive ulixertinib PO BID. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
Intervention Type
Other
Intervention Name(s)
Pharmacokinetic Study
Other Intervention Name(s)
PHARMACOKINETIC, PK Study
Intervention Description
Ancillary studies
Intervention Type
Drug
Intervention Name(s)
Ulixertinib
Other Intervention Name(s)
BVD-523, VRT752271
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
Objective Response Rate (ORR = Complete Response [CR] + Partial Response [PR]) in Pediatric Patients Treated With BVD-523FB (Ulixertinib)
Description
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.
Time Frame
From enrollment to the end of treatment, up to 2 years
Secondary Outcome Measure Information:
Title
Progression Free Survival (PFS) in Pediatric Patients Treated With Ulixertinib
Description
PFS along with the confidence intervals will be estimated using the Kaplan-Meier method.
Time Frame
From initiation of treatment to disease progression, disease recurrence, or death from any cause assessed up to 2 years
Title
Percentage of Patients Experiencing Grade 3 or 4 Adverse Events
Description
Will be graded according to Common Terminology Criteria for Adverse Events version 5.0. Any eligible patient who receives at least one dose of protocol therapy will be considered in the evaluation of toxicity.
Time Frame
From enrollment to the end of treatment, up to 2 years
Title
Preliminary Estimates of the Pharmacokinetics of Ulixertinib in Children and Adolescents With Relapsed or Refractory Cancer
Description
Will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).
Time Frame
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 Pre-specified Outcome Measures:
Title
Other Biomarkers as Predictors of Response to Ulixertinib and Whether Tumors That Harbor Different Mutations or Fusions Will Demonstrate Differential Response to Treatment
Description
Will be performed and will be summarized with simple summary statistics. All of these analyses will be descriptive in nature.
Time Frame
Up to 2 years
Title
Profiling Changes in Tumor Genomics Over Time Through Evaluation of Circulating Tumor Deoxyribonucleic Acid (DNA)
Description
Will be performed and will be summarized with simple summary statistics. All of these analyses will be descriptive in nature.
Time Frame
Up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Months
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. 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: 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kieuhoa T Vo
Organizational Affiliation
Children's Oncology Group
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Hospital of Alabama
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
Providence Alaska Medical Center
City
Anchorage
State/Province
Alaska
ZIP/Postal Code
99508
Country
United States
Facility Name
Banner Children's at Desert
City
Mesa
State/Province
Arizona
ZIP/Postal Code
85202
Country
United States
Facility Name
Banner University Medical Center - Tucson
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85719
Country
United States
Facility Name
Arkansas Children's Hospital
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72202-3591
Country
United States
Facility Name
Kaiser Permanente Downey Medical Center
City
Downey
State/Province
California
ZIP/Postal Code
90242
Country
United States
Facility Name
Loma Linda University Medical Center
City
Loma Linda
State/Province
California
ZIP/Postal Code
92354
Country
United States
Facility Name
Miller Children's and Women's Hospital Long Beach
City
Long Beach
State/Province
California
ZIP/Postal Code
90806
Country
United States
Facility Name
Children's Hospital Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
Mattel Children's Hospital UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Valley Children's Hospital
City
Madera
State/Province
California
ZIP/Postal Code
93636
Country
United States
Facility Name
UCSF Benioff Children's Hospital Oakland
City
Oakland
State/Province
California
ZIP/Postal Code
94609
Country
United States
Facility Name
Kaiser Permanente-Oakland
City
Oakland
State/Province
California
ZIP/Postal Code
94611
Country
United States
Facility Name
UCSF Medical Center-Mission Bay
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
Facility Name
Children's Hospital Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
Alfred I duPont Hospital for Children
City
Wilmington
State/Province
Delaware
ZIP/Postal Code
19803
Country
United States
Facility Name
Children's National Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
University of Florida Health Science Center - Gainesville
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
Nemours Children's Clinic-Jacksonville
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32207
Country
United States
Facility Name
University of Miami Miller School of Medicine-Sylvester Cancer Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Nicklaus Children's Hospital
City
Miami
State/Province
Florida
ZIP/Postal Code
33155
Country
United States
Facility Name
AdventHealth Orlando
City
Orlando
State/Province
Florida
ZIP/Postal Code
32803
Country
United States
Facility Name
Arnold Palmer Hospital for Children
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
Nemours Children's Hospital
City
Orlando
State/Province
Florida
ZIP/Postal Code
32827
Country
United States
Facility Name
Johns Hopkins All Children's Hospital
City
Saint Petersburg
State/Province
Florida
ZIP/Postal Code
33701
Country
United States
Facility Name
Saint Joseph's Hospital/Children's Hospital-Tampa
City
Tampa
State/Province
Florida
ZIP/Postal Code
33607
Country
United States
Facility Name
Saint Mary's Hospital
City
West Palm Beach
State/Province
Florida
ZIP/Postal Code
33407
Country
United States
Facility Name
Children's Healthcare of Atlanta - Egleston
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Memorial Health University Medical Center
City
Savannah
State/Province
Georgia
ZIP/Postal Code
31404
Country
United States
Facility Name
Saint Luke's Cancer Institute - Boise
City
Boise
State/Province
Idaho
ZIP/Postal Code
83712
Country
United States
Facility Name
University of Chicago Comprehensive Cancer Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Saint Jude Midwest Affiliate
City
Peoria
State/Province
Illinois
ZIP/Postal Code
61637
Country
United States
Facility Name
Southern Illinois University School of Medicine
City
Springfield
State/Province
Illinois
ZIP/Postal Code
62702
Country
United States
Facility Name
Riley Hospital for Children
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Ascension Saint Vincent Indianapolis Hospital
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46260
Country
United States
Facility Name
Blank Children's Hospital
City
Des Moines
State/Province
Iowa
ZIP/Postal Code
50309
Country
United States
Facility Name
University of Iowa/Holden Comprehensive Cancer Center
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Children's Hospital New Orleans
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70118
Country
United States
Facility Name
Ochsner Medical Center Jefferson
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70121
Country
United States
Facility Name
Eastern Maine Medical Center
City
Bangor
State/Province
Maine
ZIP/Postal Code
04401
Country
United States
Facility Name
Sinai Hospital of Baltimore
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21215
Country
United States
Facility Name
Johns Hopkins University/Sidney Kimmel Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Massachusetts General Hospital Cancer Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
C S Mott Children's Hospital
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Helen DeVos Children's Hospital at Spectrum Health
City
Grand Rapids
State/Province
Michigan
ZIP/Postal Code
49503
Country
United States
Facility Name
Bronson Methodist Hospital
City
Kalamazoo
State/Province
Michigan
ZIP/Postal Code
49007
Country
United States
Facility Name
Children's Hospitals and Clinics of Minnesota - Minneapolis
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55404
Country
United States
Facility Name
University of Minnesota/Masonic Cancer Center
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Mayo Clinic in Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
University of Mississippi Medical Center
City
Jackson
State/Province
Mississippi
ZIP/Postal Code
39216
Country
United States
Facility Name
Children's Mercy Hospitals and Clinics
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Facility Name
Cardinal Glennon Children's Medical Center
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63104
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Mercy Hospital Saint Louis
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63141
Country
United States
Facility Name
Children's Hospital and Medical Center of Omaha
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68114
Country
United States
Facility Name
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Morristown Medical Center
City
Morristown
State/Province
New Jersey
ZIP/Postal Code
07960
Country
United States
Facility Name
Saint Peter's University Hospital
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08901
Country
United States
Facility Name
Albany Medical Center
City
Albany
State/Province
New York
ZIP/Postal Code
12208
Country
United States
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Facility Name
The Steven and Alexandra Cohen Children's Medical Center of New York
City
New Hyde Park
State/Province
New York
ZIP/Postal Code
11040
Country
United States
Facility Name
Laura and Isaac Perlmutter Cancer Center at NYU Langone
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
NYP/Weill Cornell Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
University of Rochester
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
State University of New York Upstate Medical University
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Facility Name
Mission Hospital
City
Asheville
State/Province
North Carolina
ZIP/Postal Code
28801
Country
United States
Facility Name
Carolinas Medical Center/Levine Cancer Institute
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28203
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
Nationwide Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Facility Name
Dayton Children's Hospital
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45404
Country
United States
Facility Name
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43606
Country
United States
Facility Name
University of Oklahoma Health Sciences Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Legacy Emanuel Children's Hospital
City
Portland
State/Province
Oregon
ZIP/Postal Code
97227
Country
United States
Facility Name
Oregon Health and Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Geisinger Medical Center
City
Danville
State/Province
Pennsylvania
ZIP/Postal Code
17822
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Children's Hospital of Pittsburgh of UPMC
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Facility Name
BI-LO Charities Children's Cancer Center
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29605
Country
United States
Facility Name
Sanford USD Medical Center - Sioux Falls
City
Sioux Falls
State/Province
South Dakota
ZIP/Postal Code
57117-5134
Country
United States
Facility Name
East Tennessee Childrens Hospital
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37916
Country
United States
Facility Name
Saint Jude Children's Research Hospital
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38105
Country
United States
Facility Name
Vanderbilt University/Ingram Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Dell Children's Medical Center of Central Texas
City
Austin
State/Province
Texas
ZIP/Postal Code
78723
Country
United States
Facility Name
Medical City Dallas Hospital
City
Dallas
State/Province
Texas
ZIP/Postal Code
75230
Country
United States
Facility Name
UT Southwestern/Simmons Cancer Center-Dallas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Cook Children's Medical Center
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Children's Hospital of San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78207
Country
United States
Facility Name
Methodist Children's Hospital of South Texas
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
University of Texas Health Science Center at San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Scott and White Memorial Hospital
City
Temple
State/Province
Texas
ZIP/Postal Code
76508
Country
United States
Facility Name
Primary Children's Hospital
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84113
Country
United States
Facility Name
University of Vermont and State Agricultural College
City
Burlington
State/Province
Vermont
ZIP/Postal Code
05405
Country
United States
Facility Name
Children's Hospital of The King's Daughters
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23507
Country
United States
Facility Name
Virginia Commonwealth University/Massey Cancer Center
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Facility Name
Seattle Children's Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Facility Name
Providence Sacred Heart Medical Center and Children's Hospital
City
Spokane
State/Province
Washington
ZIP/Postal Code
99204
Country
United States
Facility Name
Madigan Army Medical Center
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98431
Country
United States
Facility Name
University of Wisconsin Carbone Cancer Center
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
Facility Name
Children's Hospital of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
San Jorge Children's Hospital
City
San Juan
ZIP/Postal Code
00912
Country
Puerto Rico
Facility Name
University Pediatric Hospital
City
San Juan
ZIP/Postal Code
00926
Country
Puerto Rico

12. IPD Sharing Statement

Citations:
PubMed Identifier
31401903
Citation
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.
Results Reference
derived

Learn more about this trial

Ulixertinib in Treating Patients With Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial)

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