A phase I study of histone deacetylase inhibitor, pracinostat (SB939), in pediatric patients with refractory solid tumors: IND203 a trial of the NCIC IND program/C17 pediatric phase I consortium. Issue 11 (25th July 2013)

• Record Type: Journal Article
• Authors: Zorzi, Alexandra P.; Bernstein, Mark; Samson, Yvan; Wall, Donna A.; Desai, Sunil; Nicksy, Darcy; Wainman, Nancy; Eisenhauer, Elizabeth; Baruchel, Sylvain
• Is Part Of: Pediatric blood & cancer. Volume 60:Issue 11(2013:Nov.)
• Page Start: 1868
• Page End: 1874
• Publication Date: 2013-07-25
• Subjects: Tumors in children -- Periodicals; Blood -- Diseases -- Periodicals; Cancer in children -- Periodicals; 618.92
• DOI: 10.1002/pbc.24694
• Languages: English
• ISSNs: 1545-5009

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="pbc24694-sec-0001" sec-type="section"> <title>Background</title> <p>Pracinostat (SB939) is a potent oral inhibitor of class 1, 2, and 4 histone deacetylases (HDAC). The adult recommended phase II dose (RP2D) is 60 mg po three times per week (t.i.w.) for 3 weeks every 4 weeks. This study assessed the toxicities and pharmacokinetics of pracinostat and determined the RP2D in children with refractory solid tumors.</p> </sec> <sec id="pbc24694-sec-0002" sec-type="section"> <title>Methods</title> <p>Pediatric patients with refractory solid tumors were treated with oral pracinostat t.i.w. for 3 consecutive weeks, followed by 1 week off dosing. Three dose levels—25, 35, and 45 mg/m<sup>2</sup> were evaluated using a standard 3 + 3 cohort design. Pharmacokinetic (PK) studies were optional.</p> </sec> <sec id="pbc24694-sec-0003" sec-type="section"> <title>Results</title> <p>Twelve patients were enrolled. The most common diagnosis was Ewing sarcoma. Most adverse events (AEs) were hematological with five (40%) patients experiencing grade 3 neutropenia. Non‐hematological AEs were generally grade 1. No dose limiting toxicities occurred. More hematological and non‐hematological AEs occurred at 45 mg/m<sup>2</sup>: Two of five patients experienced Grade 3 neutropenia and one each Grade 3 thrombocytopenia and leucopenia, Grade 1 fatigue and anorexia occurred in three. The RP2D was declared to be 45 mg/m<sup>2</sup> (comparable to an adult dose of 80 mg). One patient had a best response of stable disease (duration of 2.9 months). Three patients on 25 mg/m<sup>2</sup> and one each on 35 and 45 mg/m<sup>2</sup> participated in the PK study. No dose related changes in C<sub>max</sub> or AUC occurred.</p> </sec> <sec id="pbc24694-sec-0004" sec-type="section"> <title>Conclusions</title> <p>Pracinostat is reasonably well tolerated in children with refractory solid tumors. The RP2D is 45 mg/m<sup>2</sup>. Pediatr Blood Cancer 2013;60:1868–1874. © 2013 Wiley Periodicals, Inc.</p> </sec> </abstract>