Clinical Trial: Entinostat in Treating Pediatric Patients With Recurrent or Refractory Solid Tumors

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: 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

Brief Summary: 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.

Detailed Summary:

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. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity.


Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

  • Antitumor activity of entinostat [ Time Frame: Up to 12 months ]
  • Change in histone H3 and H4 acetylation assessed in PBMC [ Time Frame: Up to 12 months ]
  • Changes in pharmacokinetic (PK) parameters [ Time Frame: Pre-dose on days 1, 8, and 22 and 1, 3 ,6, 24, 48 and 96 hours post-dose on day 1, and day 28 ]
    A descriptive analysis of PK parameters of entinostat 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).
  • Incidence of adverse events as described and graded using CTCAE version 4.0 [ Time Frame: Up to 28 days ]
    A descriptive summary of all toxicities will be reported.
  • MTD defined as the maximum dose at which fewer than one-third of patients experience dose limiting toxicity during cycle 1 of therapy graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 28 days ]


Original Primary Outcome: Same as current

Current Secondary Outcome:

Original Secondary Outcome:

Information By: National Cancer Institute (NCI)

Dates:
Date Received: May 23, 2016
Date Started: December 2016
Date Completion:
Last Updated: May 11, 2017
Last Verified: May 2017