NEOadjuvant Trial in Adenocarcinoma of the oEsophagus and oesophagoGastric Junction International Study (Neo-AEGIS)
NCT ID: NCT01726452
Last Updated: 2022-09-30
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE3
377 participants
INTERVENTIONAL
2013-01-24
2022-08-04
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Primary Objective:
To evaluate one, two and three 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 (in particular relief of dysphagia, improvement in health related quality of life (HRQL), endoscopic regression, and CT-PET evidence of tumour response), tumour regression grade, node-positivity, post-operative pathology, disease-free survival, time to treatment failure, toxicity, post-operative complications and Health Related Quality of Life (HRQL).
Exploratory Objective(s):
Translational Research: The collection of blood and tissue samples for storage in the bio bank for future research.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Nivolumab and Ipilimumab in Treating Patients With Esophageal and Gastroesophageal Junction Adenocarcinoma Undergoing Surgery
NCT03604991
Perioperative Combination Chemotherapy Versus Chemoradiation for Locally Advanced EGJ Adenocarcinoma
NCT03961841
Neoadjuvant Treatment Modalities in Esophageal Cancer
NCT04821843
Ajuvant Chemotherapy and Immunotherapy in Patients With Esophageal, Esophageal- Gastric Junction Cancer
NCT04688801
Neoadjuvant RCT Versus CT for Patients With Locally Advanced, Potentially Resectable Adenocarcinoma of the GEJ
NCT04375605
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Patients with cT2-3 N0-1 M0 adenocarcinoma of the oesophagus or junction, based on clinical, CT-PET, and EUS staging, will be randomised to the modified MAGIC (ECF/ECX or EOF/EOX) or FLOT regimen and chemotherapy regimen versus the CROSS neoadjuvant chemo radiation protocol prior to surgery. Patients will be randomised to either Arm A (modified MAGIC or FLOT chemotherapy only and surgery) or Arm B (CROSS protocol: chemotherapy with radiation therapy and surgery as per multimodal protocol).
Eligible patients will be randomised in a 1:1 fashion between the modified MAGIC or FLOT regimen or the CROSS protocol.
Exploratory Study- Translational Research :
The collection of blood and tissue samples for storage in the bio bank for future research.
Patients enrolled in this trial at the St James's' Hospital site, will be invited to consent to having some of their tissue and blood taken for use in future research studies. Following consent from the patient, tissue biopsy of tumour and/or normal oesophageal tissue will be obtained for research at the same time as that biopsied for histological diagnosis. In addition, tumour and/or normal tissue will also be obtained following surgical resection. Patient blood samples will also be obtained, both before and during treatment. The identification of both tumour and circulating biomarkers will increase knowledge of the molecular mechanism(s) underlying treatment response in oesophageal cancer and may facilitate the identification of biomarkers predicting patient response to treatment.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
A (Modified MAGIC) OR Arm A: FLOT
Modified MAGIC: The modified MAGIC regimen encompasses 3 cycles of chemotherapy pre-surgery and 3 cycles post-surgery. The regimen is a combination of epirubicin, cisplatin or oxaliplatin and a choice of 5-fluorouracil or capecitabine. Each cycle lasts 21 days.
FLOT: The FLOT regimen encompasses 8 cycles of chemotherapy in total , 4 cycles of chemotherapy pre-surgery and a further 4 cycles of chemotherapy post-surgery. Each cycle of chemotherapy lasts 14 days/2 weeks.
Epirubicin
50mg/m2 on Day 1 of each cycle only (i.e. every 21 days)
Cisplatin / Oxaliplatin
Cisplatin, 60mg/m2 on day 1 of each cycle only (i.e. every 21 days). OR Oxaliplatin,130 mg/m2 on Day 1 of each cycle (i.e. every 21 days) The choice between administering Cisplatin or Oxaliplatin is at the discretion of the investigator.
5 Flourouracil/ Capecitabine
5-Flourouracil 200 mg/m2/day every day for 21 days OR Capecitabine 625 mg/m2 twice daily orally). The choice between administering 5 Flourouracil or Capecitabine is at the discretion of the investigator.
Docetaxel
Docetaxel, 50 mg/m², day 1 of each cycle (i.e. every 14 days)
Oxaliplatin
85 mg/m², day 1 of each cycle (i.e. every 14 days)
Leucovorin
200 mg/m², day 1 of each cycle (i.e. every 14 days).
5-Fluorouracil
2600 mg/m² Day 1 of each cycle (i.e. every 14 days) Dexamethasone or equivalent, 8mg, twice daily, Day before, day of and day after OR administered as per standard practice
B (CROSS)
Arm B consists of the multimodal CROSS arm, which includes a combination of chemotherapy and radiotherapy prior to surgery. The patient will receive four and a half (4.5) weeks of radiation therapy (41.4 Gy/23 fractions), and 5 weekly cycles of chemotherapy. The chemotherapy and radiotherapy will run concurrently over a 4 and a half-week period. Chemotherapy is given by intravenous infusion on days 1, 8, 15, 22 and 29. The radiation will generally commence on the 1st day of treatment and will run for 4 and a half weeks as follows: days 1-5, days 8-12, days 15-19, days 22-26 and days 29-31 inclusive.
(41.4 Gy/23 fractions)
Patient will receive 4.5 weeks of radiation therapy (41.4 Gy/23 fractions).
Paclitaxel
50mg/ m2 Paclitaxel dose administered on Days 1, 8, 15,22 and 29. Dexamethasone, Chlorphenamine and Ranitidine dose given per local standard practice. NACL infusion per local standard practice. Ondansetron dose given per local standard practice on Days 1, 8, 15, 22 and 29.
Carboplatin
Dose determined as per calculation, infused on Days 1, 8, 15, 22 and 29
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Epirubicin
50mg/m2 on Day 1 of each cycle only (i.e. every 21 days)
Cisplatin / Oxaliplatin
Cisplatin, 60mg/m2 on day 1 of each cycle only (i.e. every 21 days). OR Oxaliplatin,130 mg/m2 on Day 1 of each cycle (i.e. every 21 days) The choice between administering Cisplatin or Oxaliplatin is at the discretion of the investigator.
5 Flourouracil/ Capecitabine
5-Flourouracil 200 mg/m2/day every day for 21 days OR Capecitabine 625 mg/m2 twice daily orally). The choice between administering 5 Flourouracil or Capecitabine is at the discretion of the investigator.
(41.4 Gy/23 fractions)
Patient will receive 4.5 weeks of radiation therapy (41.4 Gy/23 fractions).
Paclitaxel
50mg/ m2 Paclitaxel dose administered on Days 1, 8, 15,22 and 29. Dexamethasone, Chlorphenamine and Ranitidine dose given per local standard practice. NACL infusion per local standard practice. Ondansetron dose given per local standard practice on Days 1, 8, 15, 22 and 29.
Carboplatin
Dose determined as per calculation, infused on Days 1, 8, 15, 22 and 29
Docetaxel
Docetaxel, 50 mg/m², day 1 of each cycle (i.e. every 14 days)
Oxaliplatin
85 mg/m², day 1 of each cycle (i.e. every 14 days)
Leucovorin
200 mg/m², day 1 of each cycle (i.e. every 14 days).
5-Fluorouracil
2600 mg/m² Day 1 of each cycle (i.e. every 14 days) Dexamethasone or equivalent, 8mg, twice daily, Day before, day of and day after OR administered as per standard practice
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
2. CT-18FDG-PET performed in all patients for disease staging.
3. EUS in all patients unless luminal obstruction precludes sensitivity of the test.
4. Staging laparoscopy performed at the investigator's discretion for locally advanced AEG II and AEG III tumours .
5. Pre-treatment stage cT2-3, N0-3, M0.
6. Maximum tumour length should be no more than 8cm (equal to 8 cm is acceptable)
7. Male/female patients aged ≥18 years
8. ECOG Performance Status 0, 1 or 2 (Appendix F).
9. ASA I-II (Appendix F).
10. Adequate cardiac function. For all patients, an ejection fraction of \> 50% is required. If patients have a known cardiac history (e.g. known ischemic disease, cardiomyopathy) an ejection fraction \> 50% and cardiac clearance by a consultant cardiologist for major surgery and cancer therapies is required.
11. Adequate respiratory function. Patients should have pulmonary function tests completed with a minimum FEV1 ≥ 1.5L. CPEX acceptable
12. 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).
13. Adequate renal function: glomerular filtration rate \>60ml/minute calculated using the Cockcroft-Gault Formula (Appendix O).
14. Adequate liver function: serum bilirubin \<1.5x ULN; AST \<2.5x ULN and ALP \<3x ULN (ULN as per institutional standard).
15. Written informed consent must be obtained from the patient before any study-trial specific procedures are performed.
16. Women of child-bearing potential and male subjects must agree to use an effective barrier method of contraception for up to 6 months following discontinuation of therapy. Effective contraception is defined as any medically recommended (or combination of methods) as per standard of care.
17. Women of childbearing potential must have pregnancy excluded by urine or serum beta-HCG testing within 7 days prior to treatment.
Exclusion Criteria
2. Patients with advanced inoperable or metastatic oesophageal, junctional or gastric adenocarcinoma.
3. Disease length (total length of tumour plus node) greater than 10cm (up to 10 cm will be allowed) -as measured by any modality or, if appropriate, combination of modalities-, unless in the opinion of the investigator in discussion with national RT lead, it is felt that OAR constraints are likely to be achievable.
4. Any prior chemotherapy for gastrointestinal cancer.
5. Prior abdominal or thoracic, chest wall or breast radiotherapy.
6. Patients who are unfit for surgery or cancer treatments based on cardiac disease.
7. Patients with acute systemic infections.
8. Patients who are receiving treatment with sorivudine or its chemical related analogues, such as brivudine which is contraindicated with capecitabine and 5-fluorouracil administration.
9. Clinical COPD with significant obstructive airways disease classified by FEV1 \< 1.5 L or PaO2 less than 9kPa on room air
10. Known peripheral neuropathy \>Grade 1 (absence of deep tendon reflexes as the sole neurological abnormality does not render the patient ineligible).
11. Known positive tests for human immunodeficiency virus (HIV) infection, acute or chronic active hepatitis B infection.
12. 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)
13. Participation in other clinical trials of investigational or marketed agents for the treatment of oesophageal cancer or other diseases within 30 days from registration. UK sites please refer to Group Specific Appendix
14. Women who are pregnant or breastfeeding.
15. Psychiatric illness/social situations that would limit compliance with study requirements.
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Southampton Clinical Trials Unit
UNKNOWN
Region H Rigshospitalet
UNKNOWN
Centre Hospitalier Régional, Universitaire de Lille
UNKNOWN
Cancer Trials Ireland
NETWORK
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
John V. Reynolds, Professor
Role: PRINCIPAL_INVESTIGATOR
Trinity Centre, St. James's Hospital, Dublin 8, Ireland
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Rigshospitalet
Blegdamsvej 9, , Denmark
Centre Hospitalier Régional, Universitaire de Lille 2 Avenue Oscar Lambret, 59000
Lille, , France
Cork University Hospital
Cork, , Ireland
Beaumont Hospital
Dublin, , Ireland
SLRON- St Luke's Radiation Oncology Network
Dublin, , Ireland
St. James's Hospital
Dublin, , Ireland
University Hospital Galway
Galway, , Ireland
Karolinska Institutet and Karolinska University Hospital
Stockholm, , Sweden
The Royal Bournemouth Hospital
The Royal Bournemouth and Christchurch Hospitals NHS Foundation, Bournemouth, United Kingdom
Cambridge University Hospitals NHS Foundation Trust
Addenbrooke's Hospital, Box 279(s4), Cambridge Biomedical Camp, Cambridge, United Kingdom
Velindre Cancer Centre
Velindre NHS Trust, Velindre Road, Whitchurch, Cardiff, United Kingdom
University Hospitals Coventry & Warwickshire
Clifford Bridge Road, Walsgrave, Coventry, United Kingdom
Hull and East Yorkshire Hospitals NHS Trust, Castle Hill Hospital,
Cottingham, East Riding Of Yorkshire, United Kingdom
Portsmouth Hospitals NHS Trust
Southwick Hill Road, Cosham, Hampshire, United Kingdom
Mount Vernon Cancer Centre
E & N Hertfordshire NHS Trust, Rickmansworth Road, Northwood, Middlesex, United Kingdom
Nottingham City Hospital
Nottingham University Hospitals NHS Trust, Hucknall Road, Nottingham, United Kingdom
Oxford University Hospital NHS Trust Churchill Hospital
Headington, Oxfordshire, United Kingdom
University Hospital Southampton NHS Foundation Trust
Southampton General Hospital, Division A Cancer Care, Mp307, T, Southampton, United Kingdom
Royal Surrey County Hospital
Guildford, Surrey, United Kingdom
Worcestershire Royal Hospital
Worcestershire Oncology Centre, Charles Hastings Way, Worcester, United Kingdom
Belfast Health and Social Care Trust, Northern Ireland Cancer Centre, Belfast CityHospital
Belfast, , United Kingdom
The Clatterbridge Cancer Centre NHS Foundation Trust
Birkenhead, Wirral, , United Kingdom
University Hospitals Bristol NHS Foundation Trust
Bristol, , United Kingdom
University Hospital Plymouth NHS Trust
Derriford Hospital, Derriford Road, Crownhill, Plymouth, , United Kingdom
NHS Lothian, Edinburgh Cancer Centre,
Edinburgh, , United Kingdom
Beatson West of Scotland Cancer Centre
Glasgow, 1056 Great Western Road, , United Kingdom
Imperial College Healthcare NHS Trust St Mary's Hospital
London, , United Kingdom
The Newcastle upon Tyne Hospital NHS Foundation TrustFreeman Hospital, Freeman Road, High Heaton
Newcastle upon Tyne, , United Kingdom
Royal Preston Hospital
Sharoe Garoo Lane, Fulwood, Preston, , United Kingdom
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Reynolds JV, Preston SR, O'Neill B, Lowery MA, Baeksgaard L, Crosby T, Cunningham M, Cuffe S, Griffiths GO, Parker I, Risumlund SL, Roy R, Falk S, Hanna GB, Bartlett FR, Alvarez-Iglesias A, Achiam MP, Nilsson M, Piessen G, Ravi N, O'Toole D, Johnston C, McDermott RS, Turkington RC, Wahed S, Sothi S, Ford H, Wadley MS, Power D; Neo-AEGIS Investigators and Trial Group. Trimodality therapy versus perioperative chemotherapy in the management of locally advanced adenocarcinoma of the oesophagus and oesophagogastric junction (Neo-AEGIS): an open-label, randomised, phase 3 trial. Lancet Gastroenterol Hepatol. 2023 Nov;8(11):1015-1027. doi: 10.1016/S2468-1253(23)00243-1. Epub 2023 Sep 18.
Reynolds JV, Preston SR, O'Neill B, Baeksgaard L, Griffin SM, Mariette C, Cuffe S, Cunningham M, Crosby T, Parker I, Hofland K, Hanna G, Svendsen LB, Donohoe CL, Muldoon C, O'Toole D, Johnson C, Ravi N, Jones G, Corkhill AK, Illsley M, Mellor J, Lee K, Dib M, Marchesin V, Cunnane M, Scott K, Lawner P, Warren S, O'Reilly S, O'Dowd G, Leonard G, Hennessy B, Dermott RM. ICORG 10-14: NEOadjuvant trial in Adenocarcinoma of the oEsophagus and oesophagoGastric junction International Study (Neo-AEGIS). BMC Cancer. 2017 Jun 3;17(1):401. doi: 10.1186/s12885-017-3386-2.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
CTRIAL-IE (ICORG) 10-14
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.