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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|ClinicalTrials.gov Identifier: NCT03698994|
Recruitment Status : Recruiting
First Posted : October 8, 2018
Last Update Posted : June 14, 2019
|Condition or disease||Intervention/treatment||Phase|
|Advanced Malignant Solid Neoplasm ARAF Gene Mutation BRAF Gene Mutation GNA11 Gene Mutation GNAQ Gene Mutation HRAS Gene Mutation KRAS Gene Mutation MAP2K1 Gene Mutation MAPK1 Gene Mutation NF1 Gene Mutation NRAS Gene Mutation Recurrent Ependymal Tumor Recurrent Ewing Sarcoma Recurrent Glioma Recurrent Hepatoblastoma Recurrent Histiocytic and Dendritic Cell Neoplasm Recurrent Langerhans Cell Histiocytosis Recurrent Malignant Central Nervous System Neoplasm 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 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 Central Nervous System Neoplasm 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 Rhabdoid Tumor Refractory Rhabdomyosarcoma Refractory Soft Tissue Sarcoma Wilms Tumor||Other: Pharmacokinetic Study Drug: Ulixertinib||Phase 2|
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.
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.
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||49 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||October 1, 2018|
|Estimated Primary Completion Date :||December 31, 2025|
|Estimated Study Completion Date :||December 31, 2025|
Experimental: 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.
Other: Pharmacokinetic Study
- Objective response rate (ORR = complete response [CR] + partial response [PR]) in pediatric patients treated with BVD-523FB (ulixertinib) [ Time Frame: Up to 2 years ]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
- Progression free survival (PFS) in pediatric patients treated with ulixertinib [ Time Frame: From initiation of treatment to disease progression, disease recurrence, or death from any cause assessed up to 2 years ]PFS along with the confidence intervals will be estimated using the Kaplan-Meier method.
- Incidence of adverse events [ Time Frame: Up to 2 years ]Will be graded according to Common Terminology Criteria for Adverse Events version 5.0. Toxicity tables will be constructed to summarize the observed incidence by type of toxicity and grade. A patient will be counted only once for a given toxicity for the worst grade of that toxicity reported for that patient. Toxicity information recorded will include the type, severity, time of onset, time of resolution, and the probable association with the study regimen.
- Preliminary estimates of the pharmacokinetics of ulixertinib in children and adolescents with relapsed or refractory cancer [ 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 ]Will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).
- Other biomarkers as predictors of response to ulixertinib and whether tumors that harbor different mutations or fusions will demonstrate differential response to treatment [ Time Frame: Up to 2 years ]Will be performed and will be summarized with simple summary statistics. All of these analyses will be descriptive in nature.
- Profiling changes in tumor genomics over time through evaluation of circulating tumor deoxyribonucleic acid (DNA) [ Time Frame: Up to 2 years ]Will be performed and will be summarized with simple summary statistics. All of these analyses will be descriptive in nature.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03698994
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|Principal Investigator:||Kieuhoa T Vo||Children's Oncology Group|