title: Design paper: a phase II study of bevacizumab and erlotinib in patients with non-squamous non-small cell lung cancer that is refractory or relapsed after 1-2 previous treatment (BEST).
abstract: BACKGROUND
  Combination 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.
  
  
  METHODS
  Key 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.
  
  
  CONCLUSIONS
  We 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.
  
  
  BACKGROUND
  This trial was registered at the UMIN Clinical Trials Registry as UMIN000004255 (http://www.umin.ac.jp/ctr/index.htm).
authors.affiliation: Department of Clinical Trial Design and Management, Translational Research Center, Kyoto University Hospital, 54 Shogoin Kawahara-cho, Sakyoku, Kyoto 606-8507, Japan. shiro@kuhp.kyoto-u.ac.jp
authors.forename: Shiro
authors.initials: S
authors.lastname: Tanaka
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Sakamori
authors.forename: Miyuki
authors.initials: M
authors.lastname: Niimi
authors.forename: Megumi
authors.initials: M
authors.lastname: Hazama
authors.forename: Young H
authors.initials: YH
authors.lastname: Kim
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yanagihara
mesh_terms: D000328:Adult; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D000069347:Erlotinib Hydrochloride; D006801:Humans; D007564:Japan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D009154:Mutation; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D011799:Quinazolines / Q000008:administration & dosage; D012107:Research Design; D016879:Salvage Therapy; D016019:Survival Analysis; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000068258:Bevacizumab; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors