title: Target-specific randomized discontinuation trial design: a novel approach in molecular therapeutics.
abstract: OBJECTIVE
  To describe a phase II study design to evaluate the activity of novel anti-cancer agents that focuses on molecular pathogenesis rather than tumor histology.
  
  
  METHODS
  We propose an enrichment design that enrolls patients across histologies expressing target X and incorporates randomized discontinuation of drug Y after an initial treatment period to evaluate for potential cystostatic activity.
  
  
  RESULTS
  We are currently evaluating the activity of lapatinib in patients with HER-2 amplified solid tumors using the target-specific, histology-independent, randomized discontinuation design. Patients receive treatment with lapatinib for an initial 12-week period. After restaging, patients with disease progression are removed from study, patients achieving an objective response continue treatment, and patients with stable disease are randomized to continue lapatinib versus initiate treatment with placebo. The primary endpoints are to evaluate the objective response rate during the initial treatment period and to evaluate the proportion of patients progression-free 12 weeks post-randomization.
  
  
  CONCLUSIONS
  The target-specific, histology-independent, randomized discontinuation design is an attractive alternative to the traditional phase II design for the development of "targeted" therapeutics.
authors.affiliation: Translational Oncology Program, US Oncology Research, Dallas, TX, USA. Matthew.galsky@usoncology.com
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Galsky
authors.forename: Tal
authors.initials: T
authors.lastname: Zaks
authors.forename: Habib
authors.initials: H
authors.lastname: Hassani
authors.forename: Linda
authors.initials: L
authors.lastname: Vocila
authors.forename: Guru
authors.initials: G
authors.lastname: Sonpavde
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Hutson
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Von Hoff
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D006801:Humans; D000077341:Lapatinib; D016013:Likelihood Functions; D011799:Quinazolines / Q000494:pharmacology; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012107:Research Design
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D000077341:Lapatinib