A Phase II Study of Alisertib in Children with Recurrent/Refractory Solid Tumors or Leukemia: Children’s Oncology Group Phase I and Pilot Consortium (ADVL0921)

Mossé YP, Fox E, Teachey DT, Reid JM, Safgren SL, Carol H, Lock RB, Houghton PJ, Smith MA, Hall D, Barkauskas DA, Krailo M, Voss SD, Berg SL, Blaney SM, Weigel BJ. A Phase II Study of Alisertib in Children with Recurrent/Refractory Solid Tumors or Leukemia: Children’s Oncology Group Phase I and Pilot Consortium (ADVL0921). Clin Cancer Res. 2019 Jun 1;25(11):3229-3238. doi: 10.1158/1078-0432.CCR-18-2675. Epub 2019 Feb 18. PMID: 30777875; PMCID: PMC6897379.

Aurora A kinase (AAK) plays an integral role in mitotic entry, DNA damage checkpoint recovery, and centrosome and spindle maturation. Alisertib (MLN8237) is a potent and selective AAK inhibitor. In pediatric preclinical models, antitumor activity was observed in neuroblastoma, acute lymphoblastic leukemia, and sarcoma xenografts. We conducted a phase 2 trial of alisertib in pediatric patients with refractory or recurrent solid tumors or acute leukemias (). Alisertib (80 mg/m2/dose) was administered orally, daily for 7 days every 21 days. Pharmacogenomic (PG) evaluation for polymorphisms in the AURK gene and drug metabolizing enzymes (UGT1A1*28), and plasma pharmacokinetic studies (PK) were performed. Using a two-stage design, patients were enrolled to 12 disease strata (10 solid tumor and 2 acute leukemia). Response was assessed after cycle 1, then every other cycle.