A phase 1 study of eribulin mesylate (E7389), a novel microtubule targeting chemotherapeutic agent in children with refractory or recurrent solid tumors (excluding CNS), including lymphomas: a Children's Oncology Group Phase 1 Consortium study (ADVL1314).

Abstract

2567Background: Eribulin mesylate, a synthetic analog of Halichondrin B, is a novel microtubule dynamics inhibitor. It inhibits microtubule growth without effects on microtubule shortening and promotes nonproductive tubulin aggregate formation. We performed a phase 1 trial to determine the dose limiting toxicities (DLT), maximum tolerated dose (MTD) and pharmacokinetics (PK) of eribulin in children with refractory or recurrent solid tumors, including lymphomas. Methods: Eribulin was administered intravenously on days 1 and 8 in 21-day cycles. Three dose levels (1.1, 1.4 and 1.8 mg/m2/dose) were evaluated using the rolling-6 design with additional patients enrolled into a PK expansion cohort at the MTD/recommended phase 2 dose (RP2D). PK samples were obtained following the Day 1 dose of cycle 1. Results: To date, 23 patients ages 3-17 (median 14) years have been enrolled, with 21 fully evaluable for toxicity. Subjects enrolled with 10 unique tumor types the most common of which were osteosarcoma (n = 9) an...