Abstract
BackgroundCombination of erlotinib and bevacizumab is a promising regimen in advanced non-squamous non-small-cell lung cancer (NSCLC). We are conducting a single arm phase II trial which aims to evaluate the efficacy and safety of this regime as a second- or third-line chemotherapy.MethodsKey eligibility criteria were histologically or cytologically confirmed non-squamous NSCLC, stage III/IV or recurrent NSCLC not indicated radical chemoradiation, prior one or two regimen of chemotherapy, age 20 years or more, and performance status of two or less. The primary endpoint is objective response rate. The secondary endpoints include overall survival, progression-free survival, disease control rate and incidence of adverse events. This trial plans to accrue 80 patients based on a two-stage design employing a binomial distribution with an alternative hypothesis response rate of 35% and a null hypothesis threshold response rate of 20%. A subset analysis according to EGFR mutation status is planned.DiscussionWe have presented the design of a single arm phase II trial to evaluate the efficacy and safety of combination of bevacizumab and erlotinib in advanced non-squamous NSCLC patients. In particular we are interested in determining the merit of further development of this regimen and whether prospective patient selection using EGFR gene is necessary in future trials.Trial registrationThis trial was registered at the UMIN Clinical Trials Registry as UMIN000004255 (http://www.umin.ac.jp/ctr/index.htm).
Highlights
Combination of erlotinib and bevacizumab is a promising regimen in advanced non-squamous nonsmall-cell lung cancer (NSCLC)
Two large phase III trials confirmed that bevacizumab improves survival of advanced non-squamous NSCLC patients when combined with carboplatin plus paclitaxel or cisplatin plus gemcitabine as first-line chemotherapy [12,13]
A significant improvement in progression-free survival (PFS) and objective response rate (ORR) by the addition of bevacizumab with carboplatin plus paclitaxel was shown in a randomize phase II trial of Japanese patients [14]
Summary
Design and setting This study is an open-label, multi-institute, single arm phase II clinical trial. Patient registration After confirming eligibility criteria and obtaining informed consent. 1) Grade 1 to 4 pulmonary fibrosis 2) Grade 4 non-hematologic toxicity other than pulmonary fibrosis 3) Delay from prior administration over 23 days The protocol treatment is terminated if the disease progresses, serious adverse events occurs or at the patient’s refusal. PFS is defined as the time from registration to either the first event of progression of disease or death from any cause, and it is censored at the last date when patient is alive without progression. We consider that an ORR of 20% indicates no value of further investigation of the combination This trial plans to accrue 42 patients in the first stage and 80 patients in total, which provides 90% power with an alternative hypothesis ORR of 35% and a null hypothesis ORR of 20% using one-sided testing at a 5% significance level. Multiplicity is not adjusted for since this is a secondary analysis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
