A Study of MLN8237, a Novel Aurora A Kinase Inhibitor, in Patients With Advanced Solid Tumors
To determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of MLN8237 when given by mouth (PO) for a minimum of 7 and a maximum of 21 consecutive days, followed by a 14-day recovery period.
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||An Open-Label, Dose Escalation Phase 1 Study of MLN8237, a Novel Aurora A Kinase Inhibitor, in Patients With Advanced Solid Tumors|
- determine the dose-limiting toxicity of MLN8237 [ Time Frame: Duration of therapy ] [ Designated as safety issue: Yes ]
- determine the maximum tolerated dose of MLN8237 [ Time Frame: Duration of therapy ] [ Designated as safety issue: Yes ]
- describe the pharmacokinetics of MLN8237 [ Time Frame: Duration of therapy ] [ Designated as safety issue: Yes ]
- evaluate the relationship between MLN8237 exposure and inhibition of Aurora A kinase in the proliferating basal epithelial cells of the skin [ Time Frame: Duration of therapy ] [ Designated as safety issue: Yes ]
- estimate the effect of food on the PK of MLN8237 [ Time Frame: Duration of therapy ] [ Designated as safety issue: Yes ]
- describe any antitumor activity that may be observed with MLN8237 treatment [ Time Frame: Duration of therapy ] [ Designated as safety issue: Yes ]
|Study Start Date:||May 2007|
|Study Completion Date:||November 2010|
|Primary Completion Date:||August 2010 (Final data collection date for primary outcome measure)|
MLN8237 will be supplied in capsules of 5 or 25 mg and will be given on an empty stomach, with patients remaining nothing by mouth except for water and prescribed medications for 2 hours before and 1 hour after each dose. Each dose will be given by mouth with 8 ounces of water for 7 to 21 consecutive days. A 14-day recovery period will follow each dosing period regardless of its duration.
This is an open-label, multicenter, dose escalation, phase 1 study of MLN8237 in adult patients with advanced solid tumors. This study will be the first to administer MLN8237 to humans. MLN8237 will be given daily for 7 to 21 consecutive days followed by a 14-day recovery period (cycle length = 21 to 35 days). Patients will continue to receive repeated cycles of MLN8237 as long as their disease has not progressed and they have not experienced unacceptable MLN8237-related toxicity. The dose of MLN8237 will be increased in successive cohorts of 3 to 6 patients until a maximum tolerated dose of MLN8237 has been identified. Once a maximum tolerated dose has been identified for 7 consecutive days of treatment, a total of 9 to 12 patients will be treated at that dose to better define its safety, PK, and pharmacodynamics. Longer periods of dosing with MLN8237 then will be evaluated, with an increase from 7 to 14 days, and, if feasible, to 21 days. Intermediate lengths of dosing may also be evaluated. A 14-day recovery period will follow each dosing period regardless of its duration.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00500903
|United States, Tennessee|
|Sarah Cannon Research Institute (SCRI)|
|Nashville, Tennessee, United States, 37203|
|Study Director:||Medical Monitor||Millennium Pharmaceuticals, Inc.|