title: NEOSCOPE: a randomised Phase II study of induction chemotherapy followed by either oxaliplatin/capecitabine or paclitaxel/carboplatin based chemoradiation as pre-operative regimen for resectable oesophageal adenocarcinoma.
abstract: BACKGROUND
  Both oxaliplatin/capecitabine-based chemoradiation (OXCAP-RT) and carboplatin-paclitaxel based radiation (CarPac-RT) are active regimens in oesophageal adenocarcinoma, but no randomised study has compared their efficacy and toxicity. This randomised phase II "pick a winner" trial will identify the optimum regimen to take forward to a future phase III trial against neo-adjuvant chemotherapy, the current standard in the UK.
  
  
  METHODS
  Patients with resectable adenocarcinoma of the oesophagus or Siewert Type 1-2 gastro-oesophageal junction (GOJ), ≥T3 and/or ≥ N1 are eligible for the study. Following two cycles of induction OXCAP chemotherapy (oxaliplatin 130 mg/m2 D1, Cape 625 mg/m(2) D1-21, q 3 wk), patients are randomised 1:1 to OXCAP-RT (oxaliplatin 85 mg/m(2) Day 1,15,29; capecitabine 625 mg/m(2) twice daily on days of RT; RT-45 Gy/25 fractions/5 weeks) or CarPac-RT (Carboplatin AUC2 and paclitaxel 50 mg/m2 Day 1,8,15,22,29; RT-45 Gy/25 fractions/5 weeks). Restaging CT/PET-CT is performed 4-6 weeks after CRT, and a two-phase oesophagectomy with two-field lymphadenectomy is performed six to eight weeks after CRT. The primary end-point is pathological complete response rate (pCR) at resection and will include central review. Secondary endpoints include: recruitment rate, toxicity, 30-day surgical morbidity/mortality, resection margin positivity rate and overall survival (median, 3- and 5-yr OS. 76 patients (38/arm) gives 90% power and one-sided type 1 error of 10% if patients on one novel treatment have a response rate of 35% while the second treatment has a response rate of 15%. A detailed RT Quality Assurance (RTQA) programme includes a detailed RT protocol and guidance document, pre-accrual RT workshop, outlining exercise, and central evaluation of contouring and planning. This trial has been funded by Cancer Research UK (C44694/A14614), sponsored by Velindre NHS Trust and conducted through the Wales Cancer Trials Unit at Cardiff University on behalf of the NCRI Upper GI CSG.
  
  
  CONCLUSIONS
  Following encouraging results from previous trials, there is an interest in neo-adjuvant chemotherapy and CRT containing regimens for treatment of oesophageal adenocarcinoma. NEOSCOPE will first establish the efficacy, safety and feasibility of two different neo-adjuvant CRT regimens prior to a potential phase III trial.
  
  
  BACKGROUND
  Eudract No: 2012-000640-10. ClinicalTrials.gov: NCT01843829 .
authors.affiliation: CRUK MRC Oxford Institute for Radiation Oncology Gray Laboratories, University of Oxford, Old Road Campus Research Building, Oxford, UK. somnath.mukherjee@oncology.ox.ac.uk.
authors.forename: Somnath
authors.initials: S
authors.lastname: Mukherjee
authors.affiliation: Wales Cancer Trials Unit, School of Medicine, Cardiff University, Cardiff, UK. hurtcn@cardiff.ac.uk.
authors.forename: Christopher N
authors.initials: CN
authors.lastname: Hurt
authors.affiliation: South West Wales Cancer Centre, Swansea, UK. Sarah.Gwynne@wales.nhs.uk.
authors.forename: Sarah
authors.initials: S
authors.lastname: Gwynne
authors.affiliation: Cancer Care, University Hospital Southampton, Southampton, UK. A.R.Bateman@soton.ac.uk.
authors.forename: Andrew
authors.initials: A
authors.lastname: Bateman
authors.affiliation: Department of Clinical Oncology, North Wales Cancer Treatment Centre, Rhyl, UK. simon.gollins@wales.nhs.uk.
authors.forename: Simon
authors.initials: S
authors.lastname: Gollins
authors.affiliation: St James's Institute of Oncology, Leeds, UK. g.radhakrishna@nhs.net.
authors.forename: Ganesh
authors.initials: G
authors.lastname: Radhakrishna
authors.affiliation: CRUK MRC Oxford Institute for Radiation Oncology Gray Laboratories, University of Oxford, Old Road Campus Research Building, Oxford, UK. maria.hawkins@oncology.ox.ac.uk.
authors.forename: Maria
authors.initials: M
authors.lastname: Hawkins
authors.affiliation: Wales Cancer Trials Unit, School of Medicine, Cardiff University, Cardiff, UK. CanhamJ@cardiff.ac.uk.
authors.forename: Jo
authors.initials: J
authors.lastname: Canham
authors.affiliation: University Hospital of Wales, Cardiff and Vale NHS Trust, Cardiff, UK. wyn.lewis4@wales.nhs.uk.
authors.forename: Wyn
authors.initials: W
authors.lastname: Lewis
authors.affiliation: Department of Pathology, Maastricht University Medical Centre, Maastricht, The Netherlands. heike.grabsch@mumc.nl.
authors.forename: Heike I
authors.initials: HI
authors.lastname: Grabsch
authors.affiliation: CRUK MRC Oxford Institute for Radiation Oncology Gray Laboratories, University of Oxford, Old Road Campus Research Building, Oxford, UK. ricky.sharma@oncology.ox.ac.uk.
authors.forename: Ricky A
authors.initials: RA
authors.lastname: Sharma
authors.affiliation: NISCHR CRC South East Wales Research Network, Cardiff, UK. wendy.wade@wales.nhs.uk.
authors.forename: Wendy
authors.initials: W
authors.lastname: Wade
authors.affiliation: Cardiff NCRI RTTQA group, Department of Medical Physics, Velindre Cancer Centre, Cardiff, UK. Rhydian.Maggs@wales.nhs.uk.
authors.forename: Rhydian
authors.initials: R
authors.lastname: Maggs
authors.affiliation: Velindre Cancer Centre, Velindre NHS Trust, Cardiff, UK. Bethan.Tranter@wales.nhs.uk.
authors.forename: Bethan
authors.initials: B
authors.lastname: Tranter
authors.affiliation: Velindre Cancer Centre, Velindre NHS Trust, Cardiff, UK. Ashley.Roberts@CardiffandVale.wales.nhs.uk.
authors.forename: Ashley
authors.initials: A
authors.lastname: Roberts
authors.affiliation: University of Leeds, Cancer Research UK Leeds Centre, St James's University Hospital, Leeds, UK. d.sebag-montefiore@leeds.ac.uk.
authors.forename: David
authors.initials: D
authors.lastname: Sebag-Montefiore
authors.affiliation: CRUK MRC Oxford Institute for Radiation Oncology Gray Laboratories, University of Oxford, Old Road Campus Research Building, Oxford, UK. tim.maughan@oncology.ox.ac.uk.
authors.forename: Timothy
authors.initials: T
authors.lastname: Maughan
authors.affiliation: Southampton Clinical Trials Unit, Faculty of Medicine, Southampton University, Southampton General Hospital, Southampton, UK. G.O.Griffiths@soton.ac.uk.
authors.forename: Gareth
authors.initials: G
authors.lastname: Griffiths
authors.affiliation: Velindre Cancer Centre, Velindre NHS Trust, Cardiff, UK. tom.crosby@wales.nhs.uk.
authors.forename: Tom
authors.initials: T
authors.lastname: Crosby
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D059248:Chemoradiotherapy; D002985:Clinical Protocols; D003131:Combined Modality Therapy; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D006801:Humans; D011300:Preoperative Care