MLN8237 in Treating Young Patients With Recurrent or Refractory Solid Tumors or Leukemia
RATIONALE: Alisertib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase II trial is studying the side effects of and how well alisertib works in treating young patients with relapsed or refractory solid tumors or leukemia.
Brain and Central Nervous System Tumors
Childhood Germ Cell Tumor
Other: laboratory biomarker analysis
Other: pharmacological study
|Study Design:||Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of MLN8237 (IND# 102984), a Selective Aurora A Kinase Inhibitor in Children With Recurrent/Refractory Solid Tumors and Leukemias|
- Objective response rate [ Designated as safety issue: No ]
- Toxicity [ Designated as safety issue: Yes ]
- Pharmacokinetics [ Designated as safety issue: No ]
|Study Start Date:||February 2011|
|Estimated Primary Completion Date:||March 2016 (Final data collection date for primary outcome measure)|
- To determine the objective response rate in pediatric patients with relapsed or refractory solid tumors or leukemia treated with aurora A kinase inhibitor alisertib (MLN8237).
- To define and describe the toxicities of this regimen in these patients.
- To characterize the pharmacokinetics of this regimen in these patients.
- To evaluate aurora A kinase expression in tissue samples obtained at diagnosis and at relapse.
- To explore the relationship between polymorphic variations in the UDP-glucuronosyltransferase gene UGT1A1 and exposure to MLN8237.
- To assess two common polymorphic variants in the aurora A kinase gene (Phe31Ile and Val57Ile) associated with tumorigenesis.
OUTLINE: This is a multicenter study. Patients are stratified according to type of tumor ( measurable neuroblastoma vs neuroblastoma with MIBG-positive lesions vs osteosarcoma vs Ewing sarcoma/PNET vs rhabdosarcoma vs non-RMS soft tissue sarcoma vs hepatoblastoma vs rhabdoid tumor vs malignant germ cell tumor vs Wilms tumor vs AML vs ALL).
Patients receive oral alisertib once daily on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.
Plasma samples are collected from all patients at baseline and periodically during course 1 for pharmacokinetic and other studies.
After completion of study therapy, patients are followed up for 5 years.