RATIONALE: MLN8237 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase I/II trial is studying the side effects and best dose of MLN8237 and to see how well it works in treating young patients with relapsed or refractory solid tumors
1.1 Primary Aims 1.1.1 To estimate the maximum tolerated dose (MTD) and recommended Phase II dose of MLN8237 administered orally once daily for 7 days every 21 days to children with refractory solid tumors. 1.1.2 To estimate the maximum tolerated dose (MTD) and recommended Phase II dose of MLN8237 administered orally twice daily for 7 days every 21 days to children with refractory solid tumors. 1.1.3 To define and describe the toxicities of MLN8237 administered on this schedule. 1.1.4 To characterize the pharmacokinetics of MLN8237 in children with refractory cancer. 1.2 Secondary Aims 1.2.1 To preliminarily define the antitumor activity of MLN8237 within the confines of a Phase I study. 1.2.2 To obtain initial Phase II efficacy data on the anti-tumor activity of MLN8237 in children with relapsed-refractory neuroblastoma using the once daily dosing schedule. 1.2.3 To explore the relationship between polymorphic variations in the UDPglucuronyltransferase gene UGT1A1 and exposure to MLN8237. 1.2.4 To assess two common polymorphic variants in the Aurora A kinase gene (Phe31Ile and Val57Ile) thought to potentially influence tumorigenesis. 1.2.5 To preliminarily examine the relationsh
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
54
Determine maximum tolerated dose and RP2D administered once daily on Days 1-7
Time frame: Up to 21 days (1st cycle) of protocol therapy
Determine maximum tolerated dose and RP2D administered po BID on Days 1-7
Time frame: Up to 21 days (1st cycle) of protocol therapy
Adverse events as assessed by (CTCAE) version 4.0
DLT will be defined as possibly, probably or definitely attributable to MLN8237. The DLT observation period for the purposes of dose-escalation will be the first cycle of therapy
Time frame: Every 21 days (each cycle) of protocol therapy for up to 35 cycles [up to 105 weeks]
PK Profile: MLN8237 concentrations in plasma samples
single-dose AUC, trough estimation, t½ of accumulation
Time frame: 30 min after the first dose, and at 1,2, 3, 4, 6-8, 24 hours, Day 4 and 7 in Cycle 1
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.