CMTTdb

An integrated database for cancer molecular targeted thearpies

Entry Detail


General information
Database:DB00973
Objective:To assess the maximumtolerated dose (MTD), doselimiting toxicity (DLT), safety, and tolerability of the 24h continuous intravenous (CIV) infusion of MK0457, a novel panAurora kinase inhibitor, in patients with advanced solid tumors and to determine the bioavailability of an oral dose of 100 mg MK0457.
Authors:Traynor AM, et al
Title:Phase I dose escalation study of MK0457, a novel Aurora kinase inhibitor, in adult patients with advanced solid tumors.
Journal:Cancer Chemother Pharmacol
Year:2011
PMID:20386909
Trial Design
Clinical Trial Id:NCT00104351
Agent:MK0457
Target:Aurora kinase A
Serine/threonine protein kinase 12
Protooncogene tyrosineprotein kinase LCK
Cancer Type:advanced solid tumors
Cancer Subtype:advanced solid tumors
Therapy Type:mono
Therapeutic Combination Type:NA
Therapeutic Combination Content:NA
Study Type:Phase I dose escalation study
Key Patients Feature:patients with advanced solid tumors
Biomarker:NA
Biomark Analysis:NA
Control Group Info:single arm
Treatment Info:MK0457 was administered as a 24h CIV infusion every 21 days. Dose escalation proceeded per toxicity criteria. A 100mg oral dose was administered to seven patients 48 h prior to the CIV infusion dose of 64 mg/m(2)/h.
Primary End Point:maximumtolerated dose (MTD), doselimiting toxicity (DLT), safety, and tolerability
Secondary End Point:NA
Patients Number:27
Trial Results
DLT_MTD: Dose limiting toxicity at 96 mg/m2/hr included grade 4 neutropenia and grade 3 herpes zoster. The MTD was identified as 64 mg/m2/hr.
Objective Response Rate:NA
Disease Control Rate:NA
Median Time to Progression:NA
Median PFS A vs. C:NA
Median OS A vs. C:NA
Adverse Event(agent arm):The most common adverse events were nausea, vomiting, diarrhea and fatigue.
Conclusions:MK0457 was well tolerated in this schedule. Almost half the patients attained stable disease. Further development of this class of agents will likely occur in combination with other anticancer treatments.