Neoadjuvant and adjuvant chemotherapy vs. neoadjuvant chemoradiation in adenocarcinoma of the oesophagus and oesophago-gastric junction

ISRCTN	ISRCTN60280514
DOI	https://doi.org/10.1186/ISRCTN60280514
EudraCT/CTIS number	2011-001858-28
ClinicalTrials.gov number	NCT01726452
Secondary identifying numbers	CPMS 18094

Submission date: 18/02/2015
Registration date: 18/02/2015
Last edited: 15/05/2025

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

http://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-comparing-chemotherapy-before-and-after-surgery-with-chemoradiation-before-surgery-for-cancer-food-pipe-neo-aegis

Study website

Contact information

Dr Neo-AEGIS Coordinator
Scientific

Clinical Trials Unit, MP 131, Tremona Road
Southampton
SO16 6YD
United Kingdom

Email	neoaegis@soton.ac.uk

Study information

Study design	Randomized; Interventional; Design type: Process of Care, Treatment
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Other
Study type	Treatment
Participant information sheet	Not available in web format, please use contact details to request a patient information sheet
Scientific title	Neo-AEGIS (NEO-adjuvant trial in Adenocarcinoma of the oEsophagus and oesophagoGastric junction International Study): Randomised Clinical Trial of neoadjuvant and adjuvant chemotherapy (Investigator’s choice of Modified MAGIC or FLOT regimen) versus neoadjuvant chemoradiation (CROSS protocol) in adenocarcinoma of the oesophagus and oesophago-gastric junction
Study acronym	Neo-AEGIS
Study objectives	The primary objective is to compare two level-1 evidence based approaches to adenocarcinoma of the oesophagus and oesophago-gastric junction. The MAGIC study included a minority of patients with oesophageal and junctional tumours and staging and QA modalities did not encompass current standards. The CROSS trial was not specific to adenocarcinoma, and compared a multimodal regimen to surgery alone.
Ethics approval(s)	NRES Committee East Midlands – Leicester, 18/12/2014, ref: 14/EM/1284
Health condition(s) or problem(s) studied	Adenocarcinoma of the oesophagus and oesophago-gastric junction
Intervention	1. Chemotherapy: ECX/ECF or EOX/EOF v Paclitaxel/Carboplatin given concurrently with radiotherapy 2. Radiotherapy: Concurrently with paclitaxel/carboplatin chemotherapy pre-surgery 3. Surgery: Following neoadjuvant treatment
Intervention type	Other
Primary outcome measure	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 outcome measures	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.
Overall study start date	01/08/2014
Completion date	31/07/2022

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	Planned Sample Size: 540; UK Sample Size: 250
Total final enrolment	377
Key inclusion criteria	1. Histologically verified adenocarcinoma of the oesophagus or oesophagogastric junction based on OGD 2. CT- 18FDG-PET in all patients and EUS, if feasible 3. Staging laparoscopy will be performed for tumours of the abdominal oesophagus, junction and proximal stomach i.e. AEG II and AEG III (at the investigator's discretion) 4. Pre-treatment stage cT2-3, N0-3, M0 5. No prior abdominal or thoracic radiotherapy 6. Male/female patients aged >18 years 7. ECOG Performance Status 0, 1 or 2 8. ASA Grading I-II 9. Adequate cardiac function. For patients with a significant cardiac history (e.g. known ischaemic disease, cardiomyopathy) an ejection fraction >50% and cardiac clearance by a consultant cardiologist for major surgery and cancer therapies is required, if clinically indicated. Where necessary, the Chief Investigator should be consulted to discuss the patient's eligibility. 10. Adequate respiratory function. Patients should have pulmonary function tests completed with FEV1 >1.5L 11.Adequate bone marrow function: absolute neutrophil count (ANC) >1.5x109/l; white blood cell count >3x109/l; platelets > 100x109/l; haemoglobin (Hb) >9g/dl (can be post-transfusion). 12.Adequate renal function: glomerular filtration rate >60ml/minute calculated using the Cockcroft-Gault Formula 13.Adequate liver function: serum bilirubin <1.5x ULN; AST <2.5x ULN and ALP <3x ULN (ULN as per institutional standard) 14. Written informed consent must be obtained from the patient before any study specific procedures are performed
Key exclusion criteria	1. Tumours of squamous histology 2. Patients with advanced inoperable or metastatic oesophageal, junctional or gastric adenocarcinoma 3. Any prior chemotherapy for gastrointestinal cancer 4. Prior abdominal or thoracic radiation 5. Patients who are unfit for surgery or cancer treatments based on cardiac disease 6. Clinical COPD with significant obstructive airways disease classified by FEV1 < 1.5 L or PaO2 less than 9kPa on room air 7. Known peripheral neuropathy >Grade 1 (absence of deep tendon reflexes as the sole neurological abnormality does not render the patient ineligible) 8. Known positive tests for human immunodeficiency virus (HIV) infection, acute or chronic active hepatitis B infection 9. Any other malignancies within the last 5 years (other than curatively treated basal cell carcinoma of the skin and/or in situ carcinoma of the cervix)
Date of first enrolment	02/03/2015
Date of final enrolment	23/12/2020

Locations

Countries of recruitment

England
Northern Ireland
Scotland
United Kingdom
Wales

Study participating centres

Royal Surrey County Hospital (lead site)

Egerton Road
Guildford
Surrey
GU2 7XX
United Kingdom

Queen Elizabeth Medical Centre

Edgbaston
Birmingham
B15 2TH
United Kingdom

Bristol Haematology and Oncology Centre

Horfield Road
Bristol
BS2 8ED
United Kingdom

Freeman Hospital

Freeman Road
High Heaton
Newcastle Upon Tyne
Tyne and Wear
NE7 7DN
United Kingdom

Royal Infirmary of Edinburgh

51 Little France Crescent
Edinburgh
EH16 4SA
United Kingdom

Addenbrooke’s Hospital

Hills Road
Cambridge
CB2 0QQ
United Kingdom

Oxford Cancer and Haematology Centre

Churchill Hospital
Old Road
Headington
Oxford
OX3 7LE
United Kingdom

St Mary’s Hospital

Praed Street
Paddington
London
W2 1NY
United Kingdom

Royal Preston Hospital

Sharoe Green Lane North
Fulwood
Preston
PR2 9HT
United Kingdom

Beatson West of Scotland Cancer Centre

1053 Great Western Road
Glasgow
G12 0YN
United Kingdom

Clatterbridge Cancer Centre

85 Pembroke Place
Liverpool
L7 8YA
United Kingdom

Castle Road Hospital

Hull University Teaching Hospitals NHS Trust
Castle Road
Cottingham
Hull
HU16 5JQ
United Kingdom

Nottingham City Hospital

Nottingham University Hospitals
City Hospital Campus
Hucknall Road
Nottingham
NG5 1PB
United Kingdom

Mount Vernon Cancer Centre

East and North Hertfordshire NHS Trust
Rickmansworth Road
Northwood
HA6 2RN
United Kingdom

University Hospitals Coventry and Warwickshire

Clifford Bridge Road
Coventry
CV2 2DX
United Kingdom

Velindre Cancer Centre

Velindre Road
Whitchurch
Cardiff
CF14 2TL
United Kingdom

Queen Alexandra Hospital

Portsmouth Hospitals NHS Trust
Southwick Hill Road
Portsmouth
PO6 3LY
United Kingdom

Belfast City Hospital

Lisburn Road
Belfast
BT9 7AB
United Kingdom

Worcestershire Acute Hospitals NHS Trust

Woodrow Drive
Redditch
B98 7UB
United Kingdom

Sponsor information

Cancer Trials Ireland
Hospital/treatment centre

Innovation House
Old Finglas Road
Dublin
D11 KXN4
Ireland

Email	no@email.provided
"ROR"	https://ror.org/01dpkyq75

Funders

Funder type

Government

Cancer Research UK
Private sector organisation / Other non-profit organizations

Alternative name(s): CR_UK, Cancer Research UK - London, CRUK
Location: United Kingdom

Results and Publications

Intention to publish date	01/01/2024
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not expected to be made available
Publication and dissemination plan	All information relating to this study or investigational agent, and not previously published, is considered confidential and proprietary. This confidential information shall remain the sole property of ICORG and shall not be disclosed or used (except in the performance of this study) without prior written authorisation.
IPD sharing plan	Trial data are provided to the Neo-AEGIS DSMB and will be used in trial publications, however individual patient data will not be provided to external groups on request. The trial data are held at the HRB Clinical Research Facility in Galway, Ireland: http://www.nuigalway.ie/hrb_crfg/

Study outputs

Output type	Date created	Date added	Peer reviewed?	Patient-facing?
HRA research summary		28/06/2023	No	No
Results article	18/09/2023	15/01/2024	Yes	No
Plain English results	12/05/2025	15/05/2025	No	Yes

Editorial Notes

15/05/2025: Cancer Research UK plain English summary link added to study output.
15/01/2024: Publication reference and total final enrolment added.
15/03/2021: The recruitment end date was changed from 23/12/2021 to 23/12/2020.
22/01/2021: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/12/2021 to 23/12/2021.
2. The overall trial end date was changed from 31/12/2023 to 31/07/2022.
04/12/2020: Recruitment has resumed.
03/12/2020: The following changes have been made:
1. The recruitment end date has been changed from 31/12/2020 to 31/12/2021.
2. The trial website has been added.
3. Royal Preston Hospital, Beatson West of Scotland Cancer Centre, Clatterbridge Cancer Centre, Castle Road Hospital, Nottingham City Hospital, Mount Vernon Cancer Centre, University Hospitals Coventry and Warwickshire, Velindre Cancer Centre, Queen Alexandra Hospital, Belfast City Hospital and Worcestershire Acute Hospitals NHS Trust have been added to the trial participating centres.

09/07/2020: The trial contact details have been made publicly visible.
05/05/2020: Due to current public health guidance, recruitment for this study has been paused.
14/01/2020: The following changes have been made:
1. The scientific title has been changed from "Randomised clinical trial of neoadjuvant and adjuvant chemotherapy (MAGIC regimen) vs. neoadjuvant chemoradiation (CROSS protocol) in adenocarcinoma of the oesophagus and oesophago-gastric junction" to "Neo-AEGIS (NEO-adjuvant trial in Adenocarcinoma of the oEsophagus and oesophagoGastric junction International Study): Randomised Clinical Trial of neoadjuvant and adjuvant chemotherapy (Investigator’s choice of Modified MAGIC or FLOT regimen) versus neoadjuvant chemoradiation (CROSS protocol) in adenocarcinoma of the oesophagus and oesophago-gastric junction".
2. The overall trial end date has been changed from 31/12/2022 to 31/12/2023.
3. The Participant inclusion criteria: Target number of participants has been changed from "Planned Sample Size: 594; UK Sample Size: 378" to "Planned Sample Size: 540; UK Sample Size: 250".
4. The total target enrolment has been changed from 378 to 540.
5. The recruitment end date has been changed from 31/12/2019 to 31/12/2020.
25/04/2019: The condition has been changed from "Topic: Cancer; Subtopic: Upper Gastro-Intestinal Cancer; Disease: Oesophagus, Stomach" to "Adenocarcinoma of the oesophagus and oesophago-gastric junction" following a request from the NIHR.
05/04/2019: The following changes were made to the trial record:
1. The sponsor was changed from All Ireland Cooperative Oncology Research Group to Cancer Trials Ireland.
2. IPD sharing statement added.
04/04/2019: The following changes were made to the trial record:
1. The recruitment end date was changed from 02/03/2019 to 31/12/2019.
2. The overall trial end date was changed from 02/03/2022 to 31/12/2022.
2. The intention to publish date was added.