Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations (A Pediatric MATCH Treatment Trial)
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|ClinicalTrials.gov Identifier: NCT03213652|
Recruitment Status : Recruiting
First Posted : July 11, 2017
Last Update Posted : January 23, 2020
|Condition or disease||Intervention/treatment||Phase|
|Advanced Malignant Solid Neoplasm ALK Fusion Protein Expression ALK Gene Mutation Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma Recurrent Childhood Central Nervous System Neoplasm Recurrent Childhood Non-Hodgkin Lymphoma Recurrent Malignant Solid Neoplasm Recurrent Neuroblastoma Refractory Malignant Solid Neoplasm Refractory Neuroblastoma Refractory Non-Hodgkin Lymphoma Refractory Primary Central Nervous System Neoplasm ROS1 Fusion Positive ROS1 Gene Mutation||Drug: Ensartinib Other: Laboratory Biomarker Analysis Other: Pharmacological Study||Phase 2|
I. To determine the objective response rate (ORR; complete response + partial response) in pediatric patients treated with ensartinib with advanced solid tumors (including central nervous system [CNS] tumors), non-Hodgkin lymphomas or histiocytic disorders that harbor ALK or ROS1 fusions or that harbor ALK missense mutations.
I. To estimate the progression free survival in pediatric patients treated with ensartinib with advanced solid tumors (including CNS tumors), non-Hodgkin lymphomas or histiocytic disorders that harbor ALK or ROS1 fusions or that harbor ALK missense mutations.
II. To obtain information about the tolerability of ensartinib in children with relapsed or refractory cancer.
III. To provide preliminary estimates of the pharmacokinetics of ensartinib in children with relapsed or refractory cancer.
I. To evaluate other biomarkers as predictors of response to ensartinib and specifically, whether tumors that harbor different missense mutations or fusions (including the crizotinib resistant F1174L ALK variant) will demonstrate differential response to ensartinib treatment.
II. To explore approaches to profiling changes in tumor genomics over time through evaluation of circulating tumor deoxyribonucleic acid (DNA).
Patients receive ensartinib orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||98 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 Ensartinib in Patients With Tumors Harboring ALK or ROS1 Genomic Alterations|
|Actual Study Start Date :||July 24, 2017|
|Estimated Primary Completion Date :||September 30, 2024|
|Estimated Study Completion Date :||September 30, 2024|
Experimental: Treatment (ensartinib)
Patients receive ensartinib PO QD on days 1-28. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.
Other Name: X-396
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
- Objective response rate [ Time Frame: From enrollment to the end of treatment, up to 2 years ]A responder is defined as a patient who achieves a best response of partial response or complete response on the study. 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.
- Percentage of patients experiencing grade 3 or higher adverse events [ Time Frame: From enrollment to the end of treatment, up to 2 years ]Percentage of patients experiencing grade 3 or higher adverse events will be evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. All patients who receive at least one dose of protocol therapy will be considered in the evaluation of toxicity.
- Progression free survival (PFS) [ Time Frame: From the initiation of protocol treatment to the occurrence of disease progression or disease recurrence or death from any cause, assessed up to 5 years ]Progression free survival will be defined as time 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. PFS along with the confidence intervals will be estimated using the Kaplan-Meier method.
- Pharmacokinetic (PK) parameters [ Time Frame: Pre-dose, 1, 2, 4, 6-8, and 20-24 hours post day 1 dose and pre-dose, 1, 2, 4, and 6-8 hours post day 28 dose of course 1 ]A descriptive analysis of PK parameters will be performed to define systemic exposure, drug clearance, and other pharmacokinetic parameters. The PK parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).
- Biomarkers as predictors of response to ensartinib [ Time Frame: Up to 4 years ]Descriptive analysis will be performed and will be summarized with simple summary statistics.
- Changes in tumor genomic profile [ Time Frame: Up to 4 years ]Approaches to profiling changes in tumor genomics over time through evaluation of circulating tumor DNA will be explored. Descriptive analysis will be performed and will be summarized with simple summary statistics.
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): NCT03213652
|Principal Investigator:||Meredith S Irwin||Children's Oncology Group|