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The University of Southampton
Southampton Clinical Trials Unit

Neo-AEGIS Trial


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.

Trial Design

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.

Trial Status

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.

CRUK logo

This trial is funded in the UK by Cancer Research UK (award reference no. C49462/A18483)

Trial Team

Senior Trial Manager:

Kerry Longman

Trial Manager:

Daniel Griffiths

Trial Coordinator:

Abigail Fuchs

Contact information


SAE Reporting


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).

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 .

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