Selumetinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial)
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|ClinicalTrials.gov Identifier: NCT03213691|
Recruitment Status : Recruiting
First Posted : July 11, 2017
Last Update Posted : July 3, 2018
|Condition or disease||Intervention/treatment||Phase|
|Advanced Malignant Solid Neoplasm Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma BRAF Gene Mutation GNA11 Gene Mutation GNAQ Gene Mutation Histiocytosis HRAS Gene Mutation KRAS Gene Mutation NF1 Gene Mutation NRAS Gene Mutation Recurrent Childhood Central Nervous System Neoplasm Recurrent Childhood Non-Hodgkin Lymphoma Recurrent Malignant Solid Neoplasm Recurrent Neuroblastoma Refractory Central Nervous System Neoplasm Refractory Malignant Solid Neoplasm Refractory Neuroblastoma Refractory Non-Hodgkin Lymphoma||Other: Laboratory Biomarker Analysis Drug: Selumetinib||Phase 2|
I. To determine the objective response rate (ORR; complete response + partial response) in pediatric patients treated with selumetinib (AZD6244 hydrogen sulfate) 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 selumetinib (AZD6244 hydrogen sulfate) with advanced solid tumors (including CNS tumors), non-Hodgkin lymphomas or histiocytic disorders that harbor MAPK activation mutations.
II. To obtain additional information about the tolerability of selumetinib (AZD6244 hydrogen sulfate) in children with relapsed or refractory cancer.
I. To evaluate other biomarkers as predictors of response to selumetinib (AZD6244 hydrogen sulfate) and specifically, whether tumors that harbor different mutations or fusions will demonstrate differential response to selumetinib (AZD6244 hydrogen sulfate) treatment.
II. To explore approaches to profiling changes in tumor genomics over time through evaluation of circulating tumor deoxyribonucleic acid (DNA).
Patients receive selumetinib orally (PO) twice daily (BID) on days 1-28. Courses 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 Selumetinib (AZD6244 Hydrogen Sulfate) in Patients With Tumors Harboring Activating MAPK Pathway Mutations|
|Actual Study Start Date :||July 24, 2017|
|Estimated Primary Completion Date :||September 30, 2024|
|Estimated Study Completion Date :||September 30, 2024|
Experimental: Treatment (selumetinib)
Patients receive selumetinib PO BID on days 1-28. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
- Response rate [ Time Frame: 4.5 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.
- Incidence of adverse events graded by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 [ Time Frame: Up to 4.5 years ]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.
- Progression free survival (PFS) [ Time Frame: From the initiation of protocol treatment to the occurrence of any of the following events: disease progression or disease recurrence or death from any cause, assessed up to 4.5 years ]PFS along with the confidence intervals will be estimated using the Kaplan-Meier method.
- Biomarker analysis as predictors of response to selumetinib [ Time Frame: Up to 4.5 years ]A descriptive analysis will be performed and will be summarized with simple summary statistics. All of these analyses will be descriptive in nature.
- Changes in tumor genomic profile [ Time Frame: Up to 4.5 years ]A descriptive analysis 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): NCT03213691
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|Principal Investigator:||Carl Allen||Children's Oncology Group|