Tazemetostat in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With EZH2, SMARCB1, or SMARCA4 Gene Mutations (A Pediatric MATCH Treatment Trial)
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|ClinicalTrials.gov Identifier: NCT03213665|
Recruitment Status : Recruiting
First Posted : July 11, 2017
Last Update Posted : May 23, 2019
|Condition or disease||Intervention/treatment||Phase|
|Advanced Malignant Solid Neoplasm Ann Arbor Stage III Childhood Hodgkin Lymphoma Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma Ann Arbor Stage IV Childhood Hodgkin Lymphoma Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor EZH2 Gain of Function EZH2 Gene Mutation Histiocytosis Loss of BRG1 Protein Expression Loss of INI 1 Protein Expression Low Grade Glioma Recurrent Childhood Central Nervous System Neoplasm Recurrent Childhood Ependymoma Recurrent Childhood Soft Tissue Sarcoma Recurrent Ewing Sarcoma Recurrent Glioma Recurrent Hepatoblastoma Recurrent Hodgkin Lymphoma Recurrent Langerhans Cell Histiocytosis Recurrent Malignant Germ Cell Tumor Recurrent Malignant Glioma 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 Central Nervous System Neoplasm Refractory Hodgkin Lymphoma Refractory Langerhans Cell Histiocytosis Refractory Malignant Germ Cell Tumor Refractory Malignant Glioma Refractory Medulloblastoma Refractory Neuroblastoma Refractory Non-Hodgkin Lymphoma Refractory Osteosarcoma Refractory Peripheral Primitive Neuroectodermal Tumor Refractory Rhabdoid Tumor Refractory Soft Tissue Sarcoma Rhabdoid Tumor SMARCA4 Gene Inactivation SMARCB1 Gene Inactivation Stage III Soft Tissue Sarcoma AJCC v7 Stage IV Soft Tissue Sarcoma AJCC v7 Wilms Tumor||Other: Laboratory Biomarker Analysis Drug: Tazemetostat||Phase 2|
I. To determine the objective response rate (ORR; complete response + partial response) in pediatric patients treated with tazemetostat with advanced solid tumors (including central nervous system [CNS] tumors), lymphomas or histiocytic disorders that harbor gain of function mutations in EZH2, or loss of function mutations in the SWI/SNF complex subunits SMARCB1 or SMARCA4.
I. To estimate the progression-free survival in pediatric patients treated with tazemetostat that harbor gain of function mutations in EZH2, or loss of function mutations in the SWI/SNF complex subunits SMARCB1 or SMARCA4.
II. To obtain information about the tolerability of tazemetostat in children with relapsed or refractory cancer.
I. To evaluate other biomarkers as predictors of response to tazemetostat and specifically, whether tumors that harbor different missense mutations or fusions will demonstrate differential response to tazemetostat treatment.
II. To explore approaches to profiling changes in tumor genomics over time through evaluation of circulating tumor deoxyribonucleic acid (DNA).
Patients receive tazemetostat 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 Tazemetostat in Patients With Tumors Harboring Alterations in EZH2 or Members of the SWI/SNF Complex|
|Actual Study Start Date :||July 24, 2017|
|Estimated Primary Completion Date :||September 30, 2024|
|Estimated Study Completion Date :||September 30, 2024|
Experimental: Treatment (tazemetostat)
Patients receive tazemetostat 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
- Objective response rate (ORR) defined as complete response + partial response and assessed by Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Up to 2 years ]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) [ Time Frame: From start of subprotocol treatment to time of progression or death, whichever occurs first, assessed for up to 2 years ]PFS along with the confidence intervals will be estimated using the Kaplan-Meier method.
- Biomarker predictors of response to tazemetostat [ Time Frame: Up to 2 years ]Will evaluate other biomarkers as predictors of response to tazemetostat and specifically, whether tumors that harbor different missense mutations or fusions will demonstrate differential response to tazemetostat treatment. Will be performed and will be summarized with simple summary statistics and will be descriptive in nature.
- Change in tumor genomics [ Time Frame: Up to 2 years ]To explore approaches to profiling changes in tumor genomics over time through evaluation of circulating tumor deoxyribonucleic acid. Will be performed and will be summarized with simple summary statistics and 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): NCT03213665
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|Principal Investigator:||Susan N Chi||Children's Oncology Group|