Clinical Trial Update: Results From Phase 1 Entinostat Study

April 7, 2021

Andrew J. Bukowinski, MD, MS, from the Division of Pediatric Hematology/Oncology at UPMC Children’s Hospital of Pittsburgh was the principal investigator and lead author on a phase 1 study evaluating the use of entinostat to treat recurrent or refractory solid cancers in children and adolescents. The study was published in the journal Pediatric Blood & Cancer in April. 

Dr. Bukowinski serves as the site primary investigator for the Children’s Oncology Group (COG) Pediatric Early Phase Clinical Trials Network (PEP-CTN) at UPMC Children’s. 

The new trial, for which additional details can be found on ClincialTrials.gov under identifier ADVL1513, was designed to understand the pharmacokinetics, pharmacodynamics, and maximum tolerated dose of entinostat in children with refractory and recurrent solid tumors. 

Entinostat is a class I histone deacetylase (HDAC) inhibitor that has been studied in a wide variety of solid tumors in adults.

This was the first trial of entinostat in pediatric cancer patients.

Study Results - Overview

Twenty-one patients were recruited for participation in the study. The median age of participants was 14 years.

Study participants were given either 3 or 4 mg/m2 once per week for a total of four doses over a 28-day period in a rolling six-dose escalation.

There were no dose limiting toxicities in any of the patients during the first two cycles of the study at either the 3 or 4 mg level. However, all but one of the patients experienced progression of their disease during their second dose cycle and before all six cycles could be administered

Based on these findings, the 4mg/m2 dose will be the dose recommended for further study in phase 2 trials.  

Further details of the study and the clinical trial design protocol can be found at the below references.

References

1. Bukowinski A, Chang B, Reid JM, Liu X, Minard CG, Trepel JB, Lee M-J, Fox E, Weigel BJ. A Phase 1 Study of Entinostat in Children and Adolescents With Recurrent or Refractory Solid Tumors, Including CNS Tumors: Trial ADVL1513, Pediatric Early Phase-Clinical Trial Network (PEP-CTN). Pediatr Blood Canc. 2021; 68(4): e28892.

2. ClinicalTrials.gov Identifier: NCT027880804. Entinostat in Treating Pediatric Patients With Recurrent or Refractory Solid Tumors. Principal Investigator: Andrew Bukowinski; COG Phase 1 Consortium.