Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Immune System Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Diseases and Abnormalities at or Before Birth

Nervous System Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Skin and Connective Tissue Diseases

Rare Diseases

Recurrence

Glioma

Osteosarcoma

Neuroblastoma

Sarcoma

Lymphoma

Wilms Tumor

Central Nervous System Neoplasms

Medulloblastoma

Sarcoma, Ewing

Neuroectodermal Tumors, Primitive, Peripheral

Nervous System Neoplasms

Ependymoma

Rhabdomyosarcoma

Rhabdoid Tumor

Hepatoblastoma

Histiocytosis, Langerhans-Cell

Histiocytosis

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Lymphoma, Non-Hodgkin

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Disease Attributes

Neoplasms, Connective and Soft Tissue

Neoplasms, Neuroepithelial

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Myosarcoma

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Syndrome

Neoplastic Syndromes, Hereditary

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Genetic Diseases, Inborn

Lung Diseases

Lung Diseases, Interstitial

Respiratory Tract Diseases

Soft Tissue Sarcoma

Lymphosarcoma

Germ Cells Tumors

Wilms' Tumor

Ewing Sarcoma

Langerhans Cell Histiocytosis

Neuroepithelioma

Dendritic Cell Tumor

Malignant Germ Cell Tumor

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

Ulixertinib

Kieuhoa T Vo

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.

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.

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

Will be performed and will be summarized with simple summary statistics. All of these analyses will be descriptive in nature.

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.

PFS along with the confidence intervals will be estimated using the Kaplan-Meier method.

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.

Will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).

National Cancer Institute (NCI)

Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. All-Cause Mortality includes all deaths collected on the study. Ineligible patients are excluded from reporting of adverse events.

Treatment (Ulixertinib)

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Results Reporting Coordinator

Objective Response Rate (ORR = Complete Response [CR] + Partial Response [PR]) in Pediatric Patients Treated With BVD-523FB (Ulixertinib)

Progression Free Survival (PFS) in Pediatric Patients Treated With Ulixertinib

Percentage of Patients Experiencing Grade 3 or 4 Adverse Events

Preliminary Estimates of the Pharmacokinetics of Ulixertinib in Children and Adolescents With Relapsed or Refractory Cancer

Other Biomarkers as Predictors of Response to Ulixertinib and Whether Tumors That Harbor Different Mutations or Fusions Will Demonstrate Differential Response to Treatment

Profiling Changes in Tumor Genomics Over Time Through Evaluation of Circulating Tumor Deoxyribonucleic Acid (DNA)

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Ulixertinib in Treating Patients With Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial)	NCT03698994	Advanced Malign... Recurrent Epend... Recurrent Ewing... Recurrent Gliom... Recurrent Hepat... Recurrent Histi... Recurrent Lange... Recurrent Malig... Recurrent Malig... Recurrent Medul... Recurrent Neuro... Recurrent Non-H... Recurrent Osteo... Recurrent Perip... Recurrent Prima... Recurrent Rhabd... Recurrent Rhabd... Recurrent Soft ... Refractory Epen... Refractory Ewin... Refractory Glio... Refractory Hepa... Refractory Hist... Refractory Lang... Refractory Mali... Refractory Mali... Refractory Medu... Refractory Neur... Refractory Non-... Refractory Oste... Refractory Peri... Refractory Prim... Refractory Rhab... Refractory Rhab... Refractory Soft... Wilms Tumor	Pharmacokinetic... Ulixertinib	12 Months - 21 Years	National Cancer Institute (NCI)
Ulixertinib in Treating Patients With Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial)	NCT03698994	Advanced Malign... Recurrent Epend... Recurrent Ewing... Recurrent Gliom... Recurrent Hepat... Recurrent Histi... Recurrent Lange... Recurrent Malig... Recurrent Malig... Recurrent Medul... Recurrent Neuro... Recurrent Non-H... Recurrent Osteo... Recurrent Perip... Recurrent Prima... Recurrent Rhabd... Recurrent Rhabd... Recurrent Soft ... Refractory Epen... Refractory Ewin... Refractory Glio... Refractory Hepa... Refractory Hist... Refractory Lang... Refractory Mali... Refractory Mali... Refractory Medu... Refractory Neur... Refractory Non-... Refractory Oste... Refractory Peri... Refractory Prim... Refractory Rhab... Refractory Rhab... Refractory Soft... Wilms Tumor	Pharmacokinetic... Ulixertinib	12 Months - 21 Years	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for recurrent ependymal tumor