Randomised Clinical Trial of neoadjuvant and adjuvant chemotherapy (Investigator’s choice Modified MAGIC or FLOT regimen) vs. neoadjuvant chemoradiation (CROSS protocol) in adenocarcinoma of the oesophagus and oesophago-gastric junction
Patients with cT2-3 N0-3 M0 adenocarcinoma of the oesophagus or junction, based on clinical, CT-PET, and EUS staging, will be randomised to the MAGIC/FLOT chemotherapy regimen versus the CROSS neoadjuvant chemoradiation protocol prior to surgery. Patients will be randomised to either Arm A (Investigator’s choice Modified MAGIC or FLOT regimen of chemotherapy only and surgery) or Arm B (CROSS protocol: chemotherapy with radiation therapy and surgery as per multimodal protocol). For patients that have been randomised to Arm A the treating clinician will be able to choose between the modified MAGIC or FLOT regimen as per their institution’s standard of care treatment.
Primary Objective:
To evaluate 1, 2 and 3 year survival of patients treated with resection plus neoadjuvant and adjuvant chemotherapy, versus resection plus neoadjuvant chemo radiotherapy.
Secondary Objective(s):
To evaluate the effect of both neoadjuvant regimens on clinical and pathological response rate, tumour regression grade, surgical resection rate, node-positivity, post-operative pathology, disease-free survival and time to treatment failure.
This is a multicentre phase III open-labelled, randomised controlled trial. Eligible patients will be randomised in a 1:1 fashion between the investigator’s choice of Modified MAGIC (ECF/ECX or EOF/EOX) or FLOT regimen, or the multimodality therapy (CROSS protocol) with a modernised design and delivery of radiation therapy.
Closed for recruitment
Willing patients whom are eligible to consent must be male/female aged >18 years, have histologically verified adenocarcinoma of the oesophagus or oesophago-gastric junction based on OGD with adequate cardiac, respiratory, renal and liver functions.
Patients with advanced inoperable or metastatic oesophageal, junctional or gastric adenocarcinoma will be deemed ineligible, along with patients with prior chemotherapy for gastrointestinal cancer and/or other malignancies within the last 5 years.
This trial is funded in the UK by Cancer Research UK (award reference no. C49462/A18483)
Kerry Longman
Daniel Griffiths
Trial Coordinator:
Abigail Fuchs
Email: neoaegis@soton.ac.uk
Email: ctu@soton.ac.uk
Neo-AEGIS - eCRF Completion Guidelines v5 07-July-2019
Neo-AEGIS - Appendix to eCRF Completion Guidelines_COVID 19 Protocol non-compliance_V2 07-Jul-2020
Neo-AEGIS - Event Driven Forms including EORTC QoL Forms
Neo-AEGIS - Guidelines for Completion of the SAE Reporting Form v1
Neo-AEGIS - IMP Dispensing Labelling Procedures v3 21-Oct-2019
Neo-AEGIS - MACRO User Management Access Form
Neo-AEGIS - Master Patient List
Neo-AEGIS - NHS Number Collection v2 01-Aug-2019
Neo-AEGIS - Pregnancy Reporting Form v1
Neo-AEGIS - Protocol v12 27-Jul-2020
Neo-AEGIS - Pharmacy Manual v4 11-Feb-2020
Neo-AEGIS - Radiotherapy Planning guidance v2 27-Feb-2018
Neo-AEGIS - Site Delegation Log v2
Neo-AEGIS - Protocol v12 Study Training Record v5 02 June 2020
Neo-AEGIS - Protocol v12 Training Session Record_v1 02-Jun-2020
Neo-AEGIS - UK GP Letter v4 28-Oct-2020
Neo-AEGIS - UK Group Specific Appendix v6 27-Jul-2020
J V Reynolds, S R Preston, et al. ICORG 10-14: NEOadjuvant trial in Adenocarcinoma of the oEsophagus and oesophagoGastric junction International Study (Neo-AEGIS). https://pubmed.ncbi.nlm.nih.gov/28578652/
Neo-AEGIS (Neoadjuvant trial in Adenocarcinoma of the Esophagus and Esophago-Gastric Junction International Study): Preliminary results of phase III RCT of CROSS versus perioperative chemotherapy (Modified MAGIC or FLOT protocol). Oral abstract presentation at the American Society of Clinical Oncology (ASCO) Annual Meeting, June 2021. ASCO abstract #4004 .