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

Somnath Mukherjee, Christopher N Hurt, Sarah Gwynne, Andrew Bateman, Simon Gollins, Ganesh Radhakrishna, Maria Hawkins, Jo Canham, Wyn Lewis, Heike I Grabsch, Ricky A Sharma, Wendy Wade, Rhydian Maggs, Bethan Tranter, Ashley Roberts, David Sebag-Montefiore, Timothy Maughan, Gareth Griffiths, Tom Crosby

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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/DESIGN 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. DISCUSSION 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. TRIAL REGISTRATION Eudract No: 2012-000640-10. ClinicalTrials.gov: NCT01843829 .
Original languageEnglish
Article number48
Number of pages9
JournalBMC Cancer
Volume15
Issue number48
DOIs
Publication statusPublished - 2015

Cite this

Mukherjee, S., Hurt, C. N., Gwynne, S., Bateman, A., Gollins, S., Radhakrishna, G., Hawkins, M., Canham, J., Lewis, W., Grabsch, H. I., Sharma, R. A., Wade, W., Maggs, R., Tranter, B., Roberts, A., Sebag-Montefiore, D., Maughan, T., Griffiths, G., & Crosby, T. (2015). 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. BMC Cancer, 15(48), [48]. https://doi.org/10.1186/s12885-015-1062-y