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Antineoplastic Agents

All Drugs and Chemicals

Entinostat

Histone Deacetylase Inhibitors

Enzyme Inhibitors

Patients receive entinostat PO on days 1, 8, 15, and 22. Cycles repeat every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis

Pharmacological Study

Andrew Bukowinski

This phase I trial studies the side effects and best dose of entinostat in treating pediatric patients with solid tumors that have come back or have not responded to treatment. Entinostat may block some of the enzymes needed for cell division and it may help to kill tumor cells.

PRIMARY OBJECTIVES:

I. To estimate the maximum tolerated dose (MTD) and/or recommended phase 2 dose of entinostat administered as a single-agent, once weekly to children with recurrent or refractory solid tumors.

II. To define and describe the toxicities of entinostat administered as a single agent, once weekly to children with recurrent or refractory solid tumors.

III. To characterize the pharmacokinetics of entinostat in children with recurrent or refractory cancer.

SECONDARY OBJECTIVES:

I. To preliminarily define the antitumor activity of entinostat within the confines of a phase 1 study.

II. To assess change in histone H3 and H4 acetylation in peripheral blood mononuclear cells (PBMCs) as a marker of the biologic activity of entinostat.

OUTLINE: This is a dose escalation study.

Patients receive entinostat orally (PO) on days 1, 8, 15, and 22. Cycles repeat every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity.

Entinostat in Treating Pediatric Patients With Recurrent or Refractory Solid Tumors

A Phase 1 Study of Entinostat, an Oral Histone Deacetylase Inhibitor, in Pediatric Patients With Recurrent or Refractory Solid Tumors, Including CNS Tumors and Lymphoma

The MTD/RP2D will be defined as the maximum dose at which fewer than one-third of patients experience dose limiting toxicity during cycle 1 of therapy among 6 toxicity-evaluable patients. The frequency of cycle 1 dose limiting toxicities will be summarized by dose level among patients in the dose escalation part of the study.

The frequency of patients with at least one Grade 3 or greater adverse event that are at least possibly attributable to entinostat during cycle 1 will be summarized by study part, dose level.

The median (min, max) Half-Life of entinostat stratified by study part and dose level. The half-life (t1/2) was calculated using the equation t1/2 = 0.693/λz, where the terminal elimination rate constant (λz) was determined from a least-squares regression of the log-transformed plasma concentration vs. time data for the last 3 - 4 time points.

The median (min, max) of the peak plasma concentration of entinostat stratified by study part, dose level. Time points were assessed at 0, 0.5, 1, 3, 6, 24, and 48-96 hours post-dose during cycle 1, day 1.

The median (min, max) of the total area under the plasma concentration curve of entinostat stratified by study part, dose level. Time points were assessed at 0, 0.5, 1, 3, 6, 24, and 48-96 hours post-dose during cycle 1, day 1.

The median (min, max) of the time to reach maximum plasma concentration of entinostat stratified by study part, dose level. Time points were assessed at 0, 0.5, 1, 3, 6, 24, and 48-96 hours post-dose during cycle 1, day 1.

Frequency of response to entinostat per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and/or assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR, stratified by study part and dose

Median (IQR) change in H3 acetylation in peripheral blood mononuclear cells (PBMCs) versus baseline stratified by study part, dose level.

Median (IQR) change in H4 acetylation in PBMCs versus baseline stratified by study part, dose level.

National Cancer Institute (NCI)

Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. Ineligible patients are excluded from reporting of adverse events. All-Cause Mortality includes all deaths collected on the study.

Patients with recurrent or refractory solid tumors, including lymphoma and CSN tumors, treated once weekly with entinostat administered as a single-agent at 3 mg/m2

Stratum 1 With 3 mg/m²

Patients with recurrent or refractory solid tumors, including lymphoma and CSN tumors, treated once weekly with entinostat administered as a single-agent at 4 mg/m2

Stratum 1 With 4 mg/m²

Patients with recurrent or refractory solid tumors without bone marrow involvement, including lymphoma and CSN tumors, treated once weekly with entinostat administered as a single-agent at the RP2D (4 mg/m2)

PK Part With 4 mg/m²

Total

Patients must be ≥ than 12 months and ≤ 21 years of age at the time of study enrollment, and Karnofsky \>= 50% for patients \> 16 years of age and Lansky \>= 50 for patients =\< 16 years of age.

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Results Reporting Coordinator

Patients with recurrent or refractory solid tumors, including lymphoma and CNS tumors, who receive entinostat on Days 1, 8, 15, and 22 of a 28-day cycle

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Entinostat in Treating Pediatric Patients With Recurrent or Refractory Solid Tumors	NCT02780804	Brain Stem Neop... Pineal Region N... Recurrent Lymph... Recurrent Malig... Recurrent Prima... Recurrent Visua... Refractory Lymp... Refractory Mali... Refractory Prim... Refractory Visu...	Entinostat Laboratory Biom... Pharmacological...	12 Months - 21 Years	National Cancer Institute (NCI)
Entinostat in Treating Pediatric Patients With Recurrent or Refractory Solid Tumors	NCT02780804	Brain Stem Neop... Pineal Region N... Recurrent Lymph... Recurrent Malig... Recurrent Prima... Recurrent Visua... Refractory Lymp... Refractory Mali... Refractory Prim... Refractory Visu...	Entinostat Laboratory Biom... Pharmacological...	12 Months - 21 Years	National Cancer Institute (NCI)
Entinostat in Treating Pediatric Patients With Recurrent or Refractory Solid Tumors	NCT02780804	Brain Stem Neop... Pineal Region N... Recurrent Lymph... Recurrent Malig... Recurrent Prima... Recurrent Visua... Refractory Lymp... Refractory Mali... Refractory Prim... Refractory Visu...	Entinostat Laboratory Biom... Pharmacological...	12 Months - 21 Years	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for pineal region neoplasm