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NEOadjuvant Trial in Adenocarcinoma of the oEsophagus and oesophagoGastric Junction International Study (Neo-AEGIS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01726452
Recruitment Status : Recruiting
First Posted : November 15, 2012
Last Update Posted : August 9, 2019
Southampton Clinical Trials Unit
Region H Rigshospitalet
Centre Hospitalier Régional, Universitaire de Lille
Information provided by (Responsible Party):
Cancer Trials Ireland

Brief Summary:

This is a multicentre phase III open-labelled, randomised controlled trial. Eligible patients will be randomised in a 1:1 fashion between neoadjuvant and adjuvant chemotherapy (Investigator's choice modified MAGIC (ECF/ECX or EOF/EOX) or FLOT regimen) and surgery or Arm B (CROSS protocol: chemotherapy with radiation therapy and surgery as per multimodal protocol).

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.

Condition or disease Intervention/treatment Phase
Adenocarcinoma of the Oesophagus Adenocarcinoma of the Oesophago-gastric Junction Oesophageal Tumours Junctional Tumours Oesophageal Cancer Drug: Epirubicin Drug: Cisplatin / Oxaliplatin Drug: 5 Flourouracil/ Capecitabine Radiation: (41.4 Gy/23 fractions) Drug: Paclitaxel Drug: Carboplatin Drug: Docetaxel Drug: Oxaliplatin Drug: Leucovorin Drug: 5-Fluorouracil Phase 3

Detailed Description:


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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 540 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Neo-AEGIS (NEOadjuvant Trial in Adenocarcinoma of the oEsophagus and oesophagoGastric Junction International Study): Randomised Clinical Trial of Neoadjuvant and Adjuvant Chemotherapy (Modified MAGIC or FLOT Regimen) vs. Neoadjuvant Chemoradiation (CROSS Protocol) in Adenocarcinoma of the Oesophagus and Oesophago-gastric Junction
Study Start Date : August 2012
Estimated Primary Completion Date : January 2024

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: 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.

Drug: Epirubicin
50mg/m2 on Day 1 of each cycle only (i.e. every 21 days)

Drug: 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.

Drug: 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.

Drug: Docetaxel
Docetaxel, 50 mg/m², day 1 of each cycle (i.e. every 14 days)

Drug: Oxaliplatin
85 mg/m², day 1 of each cycle (i.e. every 14 days)

Drug: Leucovorin
200 mg/m², day 1 of each cycle (i.e. every 14 days).

Drug: 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

Experimental: 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.
Radiation: (41.4 Gy/23 fractions)
Patient will receive 4.5 weeks of radiation therapy (41.4 Gy/23 fractions).

Drug: 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.

Drug: Carboplatin
Dose determined as per calculation, infused on Days 1, 8, 15, 22 and 29

Primary Outcome Measures :
  1. Overall survival [ Time Frame: At end of trial- up to 3 years in follow up ]
    Overall survival will be calculated from the date of randomisation and an event registered on the date of death from any cause. Patients lost to follow up, or those with no death recorded on the day the database is frozen, will be censored on the date of last follow up.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Histologically verified adenocarcinoma of the oesophagus or oesophago-gastric junction based on endoscopy (OGD)
  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:

  1. Tumours of squamous histology.
  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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01726452

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Contact: Cancer Trials Ireland, Innovation House, Finglas road Dublin 11 +353 1 6677211
Contact: Cancer Trials Ireland +353 1 6677211

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Rigshospitalet Recruiting
Blegdamsvej 9, Denmark, 2100 København Ø
Contact: Contact Person    +45 35 45 35 45      
Principal Investigator: Dr Lene Baeksgaard         
Centre Hospitalier Régional, Universitaire de Lille 2 Avenue Oscar Lambret, 59000 Recruiting
Lille, France
Contact: Contact Person    +33 3 20 44 41 45      
Principal Investigator: Prof Guillaume Piessen         
Belfast Health and Social Care Trust, Northern Ireland Cancer Centre, Belfast CityHospital Recruiting
Belfast, Ireland, BT9 7AB
Contact: contact    + 44 028 9097 2756      
Principal Investigator: Dr Richard Turkingon         
Cork University Hospital Active, not recruiting
Cork, Ireland
Beaumont Hospital Active, not recruiting
Dublin, Ireland
SLRON- St Luke's Radiation Oncology Network Recruiting
Dublin, Ireland
Contact: Contact Person    +353 1 4065000      
Principal Investigator: Dr Moya Cunningham         
St. James's Hospital Recruiting
Dublin, Ireland
Contact: Contact Person    +353 1 410 3000      
Principal Investigator: Prof John Reynolds         
University Hospital Galway Active, not recruiting
Galway, Ireland
United Kingdom
The Royal Bournemouth Hospital Active, not recruiting
The Royal Bournemouth And Christchurch Hospitals NHS Foundation, Bournemouth, United Kingdom, BH7 7DW
Cambridge University Hospitals NHS Foundation Trust Recruiting
Addenbrooke's Hospital, Box 279(s4), Cambridge Biomedical Camp, Cambridge, United Kingdom, CB2 0QQ
Contact: Contact Person    +44 1223 256620      
Principal Investigator: Dr Hugo Ford         
Velindre Cancer Centre Recruiting
Velindre NHS Trust, Velindre Road, Whitchurch, Cardiff, United Kingdom, CF14 2TL
Contact: Contact Person    +44 29 20 615 888      
Principal Investigator: Carys Morgan         
University Hospitals Coventry & Warwickshire Recruiting
Clifford Bridge Road, Walsgrave, Coventry, United Kingdom, CV2 2DX
Contact: Contact Person    +44 2476 966 202      
Principal Investigator: Sharmila Sothi         
Hull and East Yorkshire Hospitals NHS Trust, Castle Hill Hospital, Recruiting
Cottingham, East Riding Of Yorkshire, United Kingdom, HU16 5JQ
Contact: Contact Person    +44 23 8120 8448      
Principal Investigator: Dr Rajarshi Roy         
Portsmouth Hospitals NHS Trust Recruiting
Southwick Hill Road, Cosham, Hampshire, United Kingdom, PO6 3LY
Contact: Contact Person    +44 2392 286000      
Principal Investigator: Freddie Bartlett         
Mount Vernon Cancer Centre Recruiting
E & N Hertfordshire NHS Trust, Rickmansworth Road, Northwood, Middlesex, United Kingdom, HA6 2RN
Contact: Contact Person    +44 203 826 2063      
Principal Investigator: Mark Harrison         
Nottingham City Hospital Recruiting
Nottingham University Hospitals NHS Trust, Hucknall Road, Nottingham, United Kingdom, HG5 1PB
Contact: Contact Person    +44 115 969 1169      
Principal Investigator: Simon Parsons         
Oxford University Hospital NHS Trust Churchill Hospital Active, not recruiting
Headington, Oxfordshire, United Kingdom, OX3 7LE
University Hospital Southampton NHS Foundation Trust Active, not recruiting
Southampton General Hospital, Division A Cancer Care, Mp307, T, Southampton, United Kingdom, SO16 6YD
Royal Surrey County Hospital Recruiting
Guildford, Surrey, United Kingdom, GU2 7XX
Contact: Contact Person    +44 1483 571122      
Principal Investigator: Shaun Preston         
Worcestershire Royal Hospital Recruiting
Worcestershire Oncology Centre, Charles Hastings Way, Worcester, United Kingdom, WR5 1DD
Contact: Contact Person    +44 1905 733194      
Principal Investigator: Mr Martin Wadley         
The Clatterbridge Cancer Centre NHS Foundation Trust Not yet recruiting
Birkenhead, Wirral, United Kingdom, CH63 4JY
Contact: Dr.Raj Sripadam    +44 151 556 5000      
University Hospitals Bristol NHS Foundation Trust Recruiting
Bristol, United Kingdom, BS2 8ED
Contact: Contact Person    +44 117 342 0231      
Principal Investigator: Dr Stephen Falk         
University Hospital Plymouth NHS Trust Not yet recruiting
Derriford Hospital, Derriford Road, Crownhill, Plymouth, United Kingdom, PL6 8DH
Contact: Dr. Geoff Cogill    +44 1752 517731      
NHS Lothian, Edinburgh Cancer Centre, Recruiting
Edinburgh, United Kingdom, EH4 2XU
Contact: Contact Person    +44 131 242 3327      
Principal Investigator: Dr Sorcha Campbell         
Beatson West of Scotland Cancer Centre Not yet recruiting
Glasgow, 1056 Great Western Road, United Kingdom, G12 0YN
Contact: Dr. David McIntosh    +44 141 301 7222      
Imperial College Healthcare NHS Trust St Mary's Hospital Recruiting
London, United Kingdom, W2 1NY
Contact: Contact Person    +44 20 3312 6666      
Principal Investigator: Prof George Hanna         
The Newcastle upon Tyne Hospital NHS Foundation TrustFreeman Hospital, Freeman Road, High Heaton Recruiting
Newcastle upon Tyne, United Kingdom, NE7 7DN
Contact: Contact Person    +44 191 233 6161      
Principal Investigator: Prof Michael Griffin         
Royal Preston Hospital Not yet recruiting
Sharoe Garoo Lane, Fulwood, Preston, United Kingdom, PR2
Contact: Dr. Catherine Mitchell    +44 1772 522924      
Sponsors and Collaborators
Cancer Trials Ireland
Southampton Clinical Trials Unit
Region H Rigshospitalet
Centre Hospitalier Régional, Universitaire de Lille
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Principal Investigator: John V. Reynolds, Professor Trinity Centre, St. James's Hospital, Dublin 8, Ireland

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Cancer Trials Ireland Identifier: NCT01726452     History of Changes
Other Study ID Numbers: CTRIAL-IE (ICORG) 10-14
First Posted: November 15, 2012    Key Record Dates
Last Update Posted: August 9, 2019
Last Verified: July 2019
Additional relevant MeSH terms:
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Esophageal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents