SYNOPSIS ............................................................................................................................... 11 2. INTRODUCTION ................................................................................................................... 24 2.1 Background................................................................................................................ 24 2.1.1 Pancreatic cancer ............................................................................................. 24 2.1.2 Rationale for the trial ...................................................................................... 24 2.1.3 Pre-clinical experience .................................................................................... 25 2.1.4 Clinical experience .......................................................................................... 27 2.2 Trial objectives .......................................................................................................... 28 2.2.1 Primary objective ............................................................................................ 28 2.2.2 Secondary objective ........................................................................................ 29 2.2.3 Exploratory objectives..................................................................................... 29 3. INVESTIGATIONAL PLAN .................................................................................................. 29 3.1 Overall trial design and plan ...................................................................................... 29 3.2 Rationale for trial design, doses and stop decisions .................................................. 44 3.2.1 Trial design ......................................................................................................