CMTTdb

An integrated database for cancer molecular targeted thearpies

Entry Detail


General information
Database:DB00897
Objective:they studied the safety, clinical activity, and pharmacokinetics (PK) of AG013736, an oral receptor tyrosine kinase inhibitor of vascular endothelial cell growth factor, plateletderived growth factor, and cKit, in patients with advanced cancer.
Authors:Rugo HS, et al
Title:Phase I trial of the oral antiangiogenesis agent AG013736 in patients with advanced solid tumors: pharmacokinetic and clinical results.
Journal:J Clin Oncol.
Year:2005
PMID:16027439
Trial Design
Clinical Trial Id:NA
Agent:AG013736
Target:Macrophage colonystimulating factor 1
Vascular endothelial growth factor receptor 2
Plateletderived growth factor receptor
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 trial
Key Patients Feature:All patients were more than and equal to 18 years of age with histologically confirmed advanced nonhematologic cancer refractory to standard therapy or for which no effective therapy was available.
Biomarker:NA
Biomark Analysis:NA
Control Group Info:single arm
Treatment Info:Patients received fixed doses of AG013736 orally in 28day cycles. In the first cohort, patients initially received two single test doses of AG013736 (10 and 30 mg); subsequent dosing was determined by individual PK parameters. Doses in subsequent cohorts were assigned by using a traditional doseescalation/deescalation rule based on observed toxicities in the current and previous cohorts. PK analysis included evaluation of the effect of food and antacid.
Primary End Point:DLT¡¢MTD¡¢PK
Secondary End Point:NA
Patients Number:36
Trial Results
DLT_MTD: The doselimiting toxicities observed included hypertension, hemoptysis, and stomatitis and were seen primarily at the higher dose levels.The MTD and recommendedphase II dose of AG013736 is 5 mg BID in the fasted state
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):NA
Conclusions: In this study, they have demonstrated clinical activity and safety of AG013736 in patients with advanced solid tumors and identified the dose forphase II testing. The uniquephase I study design allotheyd early identification of important absorption and metabolic issues critical tophase II testing of this agent.