Alisertib in Treating Young Patients With Recurrent or Refractory Solid Tumors or Leukemia
Previously Treated Childhood Rhabdomyosarcoma
Recurrent Childhood Acute Lymphoblastic Leukemia
Recurrent Childhood Acute Myeloid Leukemia
Recurrent Childhood Malignant Germ Cell Tumor
Recurrent Childhood Rhabdomyosarcoma
Recurrent Childhood Soft Tissue Sarcoma
Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor
Recurrent Wilms Tumor and Other Childhood Kidney Tumors
Other: pharmacological study
Other: laboratory biomarker analysis
|Study Design:||Intervention Model: Single Group Assignment
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 [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]Response rates will be calculated as the percent of evaluable patients who are responders, and confidence intervals will be constructed accounting for the two-stage design.
- Incidence of adverse events graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]Toxicity tables constructed to summarize the observed incidence in each reporting period by type of toxicity and grade. Relative frequency of each type of toxicity quantified as the number of toxicity-evaluable cycles in which the AE was noted at >= grade 3 considered by the treating physician to be possibly, probably or definitely related to alisertib divided by the number toxicity-evaluable cycles administered to patients enrolled on the trial. In addition to the tabular presentation of the data, any adverse experience that results in the filing of an AdEERS report will be identified.
- Pharmacokinetic parameters of alisertib, including systemic exposure, drug clearance, and other pharmacokinetic parameters [ Time Frame: During the first cycle prior to drug administration and on days 1, 4, and 7 ] [ Designated as safety issue: No ]The PK parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).
|Study Start Date:||February 2011|
|Primary Completion Date:||January 2014 (Final data collection date for primary outcome measure)|
Experimental: Treatment (alisertib)
Patients receive alisertib PO QD on days 1-7. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.
Other Names:Other: pharmacological study
Other Name: pharmacological studiesOther: laboratory biomarker analysis
I. To determine the objective response rate to MLN8237 (alisertib) in children with relapsed or refractory solid tumors and leukemias, administered once daily for 7 days every 21 days.
I. To further define and describe the toxicities of MLN8237 administered on this schedule.
II. To further characterize the pharmacokinetics of MLN8237 in children with refractory cancer.
III. To evaluate aurora A kinase expression using immunohistochemistry in solid tumors and leukemic blasts from tissue obtained at diagnosis and, if available, at relapse.
IV. To explore the relationship between polymorphic variations in the UDP-glucuronosyltransferase gene UGT1A1 and exposure to MLN8237, and to assess 2 common polymorphic variants in the aurora A kinase gene, Phe31Ile and Val57Ile.
OUTLINE: This is a multicenter study. Patients are stratified according to type of tumor (measurable neuroblastoma vs neuroblastoma with metaiodobenzylguanidine [MIBG]-positive lesions vs osteosarcoma vs Ewing sarcoma/primitive neuroectodermal tumor [PNET] vs rhabdosarcoma vs non-rhabdomyosarcoma [RMS] soft tissue sarcoma vs hepatoblastoma vs malignant germ cell tumor vs Wilms tumor vs acute myeloid leukemia [AML] vs acute lymphoblastic leukemia [ALL] vs rhabdoid tumors).
Patients receive alisertib orally (PO) once daily (QD) 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01154816
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|Principal Investigator:||Yael Mosse||Children's Oncology Group|