CMTTdb

An integrated database for cancer molecular targeted thearpies

Entry Detail


General information
Database:DB00854
Objective:Lapatinib is a dual tyrosine kinase inhibitor that targets epidermal growth factor receptor and human epidermal growth factor receptor 2. they report on a doseescalation study of lapatinib combined with pemetrexed in secondline treatment to evaluate the safety and efficacy in advanced or metastatic non small cell lung cancer (non small cell lung cancer) and an exploratory study in which circulating cellfree thymidylate synthase ribonucleic acid (cfTSmRNA) was measured in all patients and compared with clinical benefit.
Authors:Ramlau R, et al
Title:Phase I Study of Lapatinib and Pemetrexed in the SecondLine Treatment of Advanced or Metastatic non small cell Lung Cancer With Assessment of Circulating Cell Free Thymidylate Synthase RNA as a Potential Biomarker.
Journal:Clin Lung Cancer.
Year:2015
PMID:25700774
Trial Design
Clinical Trial Id: NCT00528281
Agent:lapatinib
Target:Epidermal growth factor receptor
Receptor proteintyrosine kinase erbB2
Cancer Type:non small cell lung cancer
Cancer Subtype:advanced non smallcell lung cancer
Therapy Type:mono
Therapeutic Combination Type:NA
Therapeutic Combination Content:NA
Study Type:Phase I Study
Key Patients Feature:Eligible patients had stage IIIB or IV non small cell lung cancer after 1 previous line of chemotherapy and an Eastern Cooperative Oncology Group performance status of 0 to 2.
Biomarker:levels of cfTSmRNA
Biomark Analysis:cfTSmRNA was at the limit of detection and was not measurable in all patients. Nonsignificant trends were observed, suggesting that higher levels of cfTSmRNA are associated with poorer outcome.
Control Group Info:single arm
Treatment Info:Three dose levels (DLs) of lapatinib (daily)/pemetrexed (every 21 days) were evaluated: DL0, 1250 mg/400 mg; DL1, 1250 mg/500 mg; and DL2, 1500 mg/500 mg, respectively.
Primary End Point:The primary outcome was identification of the optimal treatment regimen.
Secondary End Point:NA
Patients Number:18
Trial Results
DLT_MTD:Eighteen patients were treated (DL0: n = 4; DL1: n = 8; DL2: n = 6).DL1 was determined as optimal after 3 doselimiting toxicities (DLTs) during the first cycle of DL2 (Grade 3 diarrhea and mucositis, Grade 4 lymphocytopenia); no other DLTs were observed.
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):Eighteen patients were treated (DL0: n = 4; DL1: n = 8; DL2: n = 6).
Conclusions:Lapatinib and pemetrexed was well tolerated, and data suggest a similar response rate to pemetrexed monotherapy