Trials / Completed
CompletedNCT03213665
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)
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
- Status
- Completed
- Phase
- Phase 2
- Study type
- Interventional
- Enrollment
- 20 (actual)
- Sponsor
- National Cancer Institute (NCI) · NIH
- Sex
- All
- Age
- 12 Months – 21 Years
- Healthy volunteers
- Not accepted
Summary
This phase II Pediatric MATCH trial studies how well tazemetostat works in treating patients with brain tumors, solid tumors, non-Hodgkin lymphoma, or histiocytic disorders that have come back (relapsed) or do not respond to treatment (refractory) and have EZH2, SMARCB1, or SMARCA4 gene mutations. Tazemetostat may stop the growth of tumor cells by blocking EZH2 and its relation to some of the pathways needed for cell proliferation.
Detailed description
PRIMARY OBJECTIVE: 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), non-Hodgkin lymphoma 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 at a dose of 520 mg/m\^2/dose twice daily for patients without any CNS involvement or 1200 mg/m\^2/dose orally twice daily for patients with CNS involvement. SECONDARY OBJECTIVES: 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. EXPLORATORY OBJECTIVES: 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). OUTLINE: Patients receive tazemetostat orally (PO) twice daily (BID) on days 1-28. 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.
Conditions
- Advanced Malignant Solid Neoplasm
- Ann Arbor Stage III Hodgkin Lymphoma
- Ann Arbor Stage III Non-Hodgkin Lymphoma
- Ann Arbor Stage IV Hodgkin Lymphoma
- Ann Arbor Stage IV Non-Hodgkin Lymphoma
- Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor
- Low Grade Glioma
- Recurrent Ependymoma
- 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 Primary Central Nervous System Neoplasm
- Recurrent Rhabdoid Tumor
- Recurrent Rhabdomyosarcoma
- Recurrent Soft Tissue Sarcoma
- Refractory Hodgkin Lymphoma
- Refractory Langerhans Cell Histiocytosis
- Refractory Malignant Germ Cell Tumor
- Refractory Malignant Glioma
- Refractory Malignant Solid Neoplasm
- Refractory Medulloblastoma
- Refractory Neuroblastoma
- Refractory Non-Hodgkin Lymphoma
- Refractory Osteosarcoma
- Refractory Peripheral Primitive Neuroectodermal Tumor
- Refractory Rhabdoid Tumor
- Refractory Soft Tissue Sarcoma
- Rhabdoid Tumor
- Stage III Soft Tissue Sarcoma AJCC v7
- Stage IV Soft Tissue Sarcoma AJCC v7
- Wilms Tumor
Interventions
| Type | Name | Description |
|---|---|---|
| DRUG | Tazemetostat | Given PO |
Timeline
- Start date
- 2017-11-13
- Primary completion
- 2022-03-31
- Completion
- 2024-12-31
- First posted
- 2017-07-11
- Last updated
- 2026-04-13
- Results posted
- 2023-04-27
Locations
117 sites across 2 countries: United States, Puerto Rico
Regulatory
- FDA-regulated drug study
Source: ClinicalTrials.gov record NCT03213665. Inclusion in this directory is not an endorsement.