Format

Send to

Choose Destination
Ann Oncol. 2011 Jan;22(1):195-201. doi: 10.1093/annonc/mdq313. Epub 2010 Jul 6.

Phase I trial of SU14813 in patients with advanced solid malignancies.

Author information

1
Department of Oncology, Hematology, BMT With Section Pneumology, Hubertus Wald Tumorzentrum, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. fiedler@uke.uni-hamburg.de

Abstract

BACKGROUND:

this phase I, open-label, dose-escalation study investigated SU14813, an oral multitargeted tyrosine kinase inhibitor, in adults with solid tumors.

PATIENTS AND METHODS:

seventy-seven patients received once-daily SU14813, either for 4 weeks followed by 1 week off treatment (schedule 4/1) or continuously [continuous daily dosing (CDD)]. The primary end point was to determine the maximum tolerated dose (MTD). Safety, pharmacokinetics, pharmacodynamics, and efficacy were assessed.

RESULTS:

MTDs were 200 mg/day on schedule 4/1 and 100 mg/day with CDD. Adverse events included fatigue (64%), diarrhea (61%), nausea (44%), anorexia (43%), and vomiting (42%). SU14813 steady state was attained by day 8. Exposure increased in a generally dose-proportional manner and SU14813 was eliminated with a mean terminal half-life of 9-34 h. Target plasma concentrations (>100 ng/ml SU14813) were achieved and sustained over 12 h at ≥ 100 mg/day. Progression-free survival among the 1 complete responder and 12 partial responders was 1.4-53.2 months. Fifteen patients remained on treatment at 1 year and 3 patients at 2 years.

CONCLUSION:

SU14813 has manageable safety and tolerability and allows once-daily continuous oral dosing. SU14813 shows dose-proportional pharmacokinetics, with target plasma concentrations achieved at doses ≥ 100 mg/day. Clinically meaningful activity with durable responses was observed, meriting further study.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00982267.

PMID:
20605934
DOI:
10.1093/annonc/mdq313
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center