title: Precision Medicine for Advanced Pancreas Cancer: The Individualized Molecular Pancreatic Cancer Therapy (IMPaCT) Trial.
abstract: OBJECTIVE
  Personalized medicine strategies using genomic profiling are particularly pertinent for pancreas cancer. The Individualized Molecular Pancreatic Cancer Therapy (IMPaCT) trial was initially designed to exploit results from genome sequencing of pancreatic cancer under the auspices of the International Cancer Genome Consortium (ICGC) in Australia. Sequencing revealed small subsets of patients with aberrations in their tumor genome that could be targeted with currently available therapies.
  
  
  METHODS
  The pilot stage of the IMPaCT trial assessed the feasibility of acquiring suitable tumor specimens for molecular analysis and returning high-quality actionable genomic data within a clinically acceptable timeframe. We screened for three molecular targets: HER2 amplification; KRAS wild-type; and mutations in DNA damage repair pathways (BRCA1, BRCA2, PALB2, ATM).
  
  
  RESULTS
  Tumor biopsy and archived tumor samples were collected from 93 patients and 76 were screened. To date 22 candidate cases have been identified: 14 KRAS wild-type, 5 cases of HER2 amplification, 2 mutations in BRCA2, and 1 ATM mutation. Median time from consent to the return of validated results was 21.5 days. An inability to obtain a biopsy or insufficient tumor content in the available specimen were common reasons for patient exclusion from molecular analysis while deteriorating performance status prohibited a number of patients from proceeding in the study.
  
  
  CONCLUSIONS
  Documenting the feasibility of acquiring and screening biospecimens for actionable molecular targets in real time will aid other groups embarking on similar trials. Key elements include the need to better prescreen patients, screen more patients, and offer more attractive clinical trial options.
authors.affiliation: The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia. Macarthur Cancer Therapy Centre, Campbelltown, New South Wales, Australia. Sydney Catalyst Translational Cancer Research Centre, University of Sydney, Camperdown, New South Wales, Australia. andrew.biankin@glasgow.ac.uk l.chantrill@garvan.org.au.
authors.forename: Lorraine A
authors.initials: LA
authors.lastname: Chantrill
authors.affiliation: The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia. Sydney Catalyst Translational Cancer Research Centre, University of Sydney, Camperdown, New South Wales, Australia. Crown Princess Mary Cancer Centre, Westmead, New South Wales, Australia.
authors.forename: Adnan M
authors.initials: AM
authors.lastname: Nagrial
authors.affiliation: The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
authors.forename: Clare
authors.initials: C
authors.lastname: Watson
authors.affiliation: The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
authors.forename: Amber L
authors.initials: AL
authors.lastname: Johns
authors.affiliation: The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
authors.forename: Mona
authors.initials: M
authors.lastname: Martyn-Smith
authors.affiliation: The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
authors.forename: Skye
authors.initials: S
authors.lastname: Simpson
authors.affiliation: The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia. Prince of Wales Hospital, Randwick, New South Wales, Australia.
authors.forename: Scott
authors.initials: S
authors.lastname: Mead
authors.affiliation: Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland.
authors.forename: Marc D
authors.initials: MD
authors.lastname: Jones
authors.affiliation: University of Sydney, New South Wales, Australia. Macquarie University Hospital, Sydney, New South Wales, Australia.
authors.forename: Jaswinder S
authors.initials: JS
authors.lastname: Samra
authors.affiliation: Department of Anatomical Pathology, Royal North Shore Hospital, Sydney, New South Wales, Australia.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Gill
authors.affiliation: Department of Anatomical Pathology, Royal North Shore Hospital, Sydney, New South Wales, Australia.
authors.forename: Nicole
authors.initials: N
authors.lastname: Watson
authors.affiliation: The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia. Sydney Catalyst Translational Cancer Research Centre, University of Sydney, Camperdown, New South Wales, Australia.
authors.forename: Venessa T
authors.initials: VT
authors.lastname: Chin
authors.affiliation: The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
authors.forename: Jeremy L
authors.initials: JL
authors.lastname: Humphris
authors.affiliation: The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia. Department of Anatomical Pathology, St. Vincent's Hospital, Darlinghurst, Sydney, New South Wales, Australia.
authors.forename: Angela
authors.initials: A
authors.lastname: Chou
authors.affiliation: Department of Anatomical Pathology, St. Vincent's Hospital, Darlinghurst, Sydney, New South Wales, Australia.
authors.forename: Belinda
authors.initials: B
authors.lastname: Brown
authors.affiliation: Department of Anatomical Pathology, St. Vincent's Hospital, Darlinghurst, Sydney, New South Wales, Australia.
authors.forename: Adrienne
authors.initials: A
authors.lastname: Morey
authors.affiliation: The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
authors.forename: Marina
authors.initials: M
authors.lastname: Pajic
authors.affiliation: Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland.
authors.forename: Sean M
authors.initials: SM
authors.lastname: Grimmond
authors.affiliation: Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland. Department of Surgery, Bankstown Hospital, Sydney, New South Wales, Australia. South Western Sydney Clinical School, Faculty of Medicine, University of NSW, Liverpool, New South Wales, Australia. West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom.
authors.forename: David K
authors.initials: DK
authors.lastname: Chang
authors.affiliation: The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia. Sydney Catalyst Translational Cancer Research Centre, University of Sydney, Camperdown, New South Wales, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Thomas
authors.affiliation: NHMRC Clinical Trials Centre, University of Sydney, Camperdown, New South Wales, Australia.
authors.forename: Lucille
authors.initials: L
authors.lastname: Sebastian
authors.affiliation: Sydney Catalyst Translational Cancer Research Centre, University of Sydney, Camperdown, New South Wales, Australia. NHMRC Clinical Trials Centre, University of Sydney, Camperdown, New South Wales, Australia.
authors.forename: Katrin
authors.initials: K
authors.lastname: Sjoquist
authors.affiliation: Sydney Catalyst Translational Cancer Research Centre, University of Sydney, Camperdown, New South Wales, Australia. NHMRC Clinical Trials Centre, University of Sydney, Camperdown, New South Wales, Australia.
authors.forename: Sonia
authors.initials: S
authors.lastname: Yip
authors.affiliation: Northern Sydney Cancer Centre, Royal North Shore Hospital, New South Wales, Australia.
authors.forename: Nick
authors.initials: N
authors.lastname: Pavlakis
authors.affiliation: Bankstown Cancer Centre, Bankstown, New South Wales, Australia.
authors.forename: Ray
authors.initials: R
authors.lastname: Asghari
authors.affiliation: Bankstown Cancer Centre, Bankstown, New South Wales, Australia.
authors.forename: Sandra
authors.initials: S
authors.lastname: Harvey
authors.affiliation: Sydney Catalyst Translational Cancer Research Centre, University of Sydney, Camperdown, New South Wales, Australia. Chris O'Brien Lifehouse, Camperdown, New South Wales, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Grimison
authors.affiliation: Sydney Catalyst Translational Cancer Research Centre, University of Sydney, Camperdown, New South Wales, Australia. NHMRC Clinical Trials Centre, University of Sydney, Camperdown, New South Wales, Australia. Chris O'Brien Lifehouse, Camperdown, New South Wales, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Simes
authors.affiliation: The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia. Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland. Department of Surgery, Bankstown Hospital, Sydney, New South Wales, Australia. South Western Sydney Clinical School, Faculty of Medicine, University of NSW, Liverpool, New South Wales, Australia. West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom. andrew.biankin@glasgow.ac.uk l.chantrill@garvan.org.au.
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Biankin
mesh_terms: D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008297:Male; D058990:Molecular Targeted Therapy / Q000379:methods*; D010190:Pancreatic Neoplasms / Q000235:genetics*; D010340:Pathology, Surgical / Q000379:methods; D010865:Pilot Projects; D016133:Polymerase Chain Reaction; D057285:Precision Medicine / Q000379:methods*; D013048:Specimen Handling / Q000379:methods