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Adenocarcinoma of the OesophagusPhase 3NCT01726452

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

A Phase 3 study testing Epirubicin, Cisplatin / Oxaliplatin and 5 Flourouracil/ Capecitabine in people with Adenocarcinoma of the Oesophagus and Adenocarcinoma of the Oesophago-gastric Junction, run by Cancer Trials Ireland at 29 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Epirubicin, Cisplatin / Oxaliplatin and 5 Flourouracil/ Capecitabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
377 participants
Where
29 sitesin 5 countries
Study dates
24 Jan 2013to 4 Aug 2022
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically verified adenocarcinoma of the oesophagus or oesophago-gastric junction based on endoscopy (OGD)
  • CT-18FDG-PET performed in all patients for disease staging.
  • EUS in all patients unless luminal obstruction precludes sensitivity of the test.
  • Staging laparoscopy performed at the investigator's discretion for locally advanced AEG II and AEG III tumours .
  • Pre-treatment stage cT2-3, N0-3, M0.
  • Maximum tumour length should be no more than 8cm (equal to 8 cm is acceptable)
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  • Male/female patients aged ≥18 years
  • ECOG Performance Status 0, 1 or 2 (Appendix F).
  • ASA I-II (Appendix F).
  • 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.
  • Adequate respiratory function. Patients should have pulmonary function tests completed with a minimum FEV1 ≥ 1.5L. CPEX acceptable
  • 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).
  • Adequate renal function: glomerular filtration rate >60ml/minute calculated using the Cockcroft-Gault Formula (Appendix O).
  • Adequate liver function: serum bilirubin <1.5x ULN; AST <2.5x ULN and ALP <3x ULN (ULN as per institutional standard).
  • Written informed consent must be obtained from the patient before any study-trial specific procedures are performed.
  • 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.
  • Women of childbearing potential must have pregnancy excluded by urine or serum beta-HCG testing within 7 days prior to treatment.

Who cannot join

  • Tumours of squamous histology.
  • Patients with advanced inoperable or metastatic oesophageal, junctional or gastric adenocarcinoma.
  • 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.
  • Any prior chemotherapy for gastrointestinal cancer.
  • Prior abdominal or thoracic, chest wall or breast radiotherapy.
  • Patients who are unfit for surgery or cancer treatments based on cardiac disease.
Show all 15Show fewer
  • Patients with acute systemic infections.
  • Patients who are receiving treatment with sorivudine or its chemical related analogues, such as brivudine which is contraindicated with capecitabine and 5-fluorouracil administration.
  • Clinical COPD with significant obstructive airways disease classified by FEV1 < 1.5 L or PaO2 less than 9kPa on room air
  • Known peripheral neuropathy >Grade 1 (absence of deep tendon reflexes as the sole neurological abnormality does not render the patient ineligible).
  • Known positive tests for human immunodeficiency virus (HIV) infection, acute or chronic active hepatitis B infection.
  • 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)
  • 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
  • Women who are pregnant or breastfeeding.
  • Psychiatric illness/social situations that would limit compliance with study requirements.

Trial locations and contacts

29 sites in 5 countries.

29 sites in 5 countries

United Kingdom21 sites

  • Cambridge University Hospitals NHS Foundation Trust

    Addenbrooke's Hospital, Box 279(s4), Cambridge Biomedical Camp, Cambridge, CB2 0QQ

  • Belfast Health and Social Care Trust, Northern Ireland Cancer Centre, Belfast CityHospital

    Belfast, BT9 7AB

  • The Clatterbridge Cancer Centre NHS Foundation Trust

    Birkenhead, Wirral, CH63 4JY

  • University Hospitals Bristol NHS Foundation Trust

    Bristol, BS2 8ED

  • University Hospitals Coventry & Warwickshire

    Clifford Bridge Road, Walsgrave, Coventry, CV2 2DX

  • Hull and East Yorkshire Hospitals NHS Trust, Castle Hill Hospital,

    Cottingham, East Riding Of Yorkshire, HU16 5JQ

  • University Hospital Plymouth NHS Trust

    Derriford Hospital, Derriford Road, Crownhill, Plymouth, PL6 8DH

  • Mount Vernon Cancer Centre

    E & N Hertfordshire NHS Trust, Rickmansworth Road, Northwood, Middlesex, HA6 2RN

  • NHS Lothian, Edinburgh Cancer Centre,

    Edinburgh, EH4 2XU

  • Beatson West of Scotland Cancer Centre

    Glasgow, 1056 Great Western Road, G12 0YN

  • Royal Surrey County Hospital

    Guildford, Surrey, GU2 7XX

  • Oxford University Hospital NHS Trust Churchill Hospital

    Headington, Oxfordshire, OX3 7LE

  • Imperial College Healthcare NHS Trust St Mary's Hospital

    London, W2 1NY

  • The Newcastle upon Tyne Hospital NHS Foundation TrustFreeman Hospital, Freeman Road, High Heaton

    Newcastle upon Tyne, NE7 7DN

  • Nottingham City Hospital

    Nottingham University Hospitals NHS Trust, Hucknall Road, Nottingham, HG5 1PB

  • Royal Preston Hospital

    Sharoe Garoo Lane, Fulwood, Preston, PR2

  • University Hospital Southampton NHS Foundation Trust

    Southampton General Hospital, Division A Cancer Care, Mp307, T, Southampton, SO16 6YD

  • Portsmouth Hospitals NHS Trust

    Southwick Hill Road, Cosham, Hampshire, PO6 3LY

  • The Royal Bournemouth Hospital

    The Royal Bournemouth and Christchurch Hospitals NHS Foundation, Bournemouth, BH7 7DW

  • Velindre Cancer Centre

    Velindre NHS Trust, Velindre Road, Whitchurch, Cardiff, CF14 2TL

  • Worcestershire Royal Hospital

    Worcestershire Oncology Centre, Charles Hastings Way, Worcester, WR5 1DD

Other trials in United Kingdom

Ireland5 sites

  • Cork University Hospital

    Cork

  • Beaumont Hospital

    Dublin

  • SLRON- St Luke's Radiation Oncology Network

    Dublin

  • St. James's Hospital

    Dublin

  • University Hospital Galway

    Galway

Other trials in Ireland

Denmark1 site

  • Rigshospitalet

    Blegdamsvej 9, 2100 København Ø

Other trials in Denmark

France1 site

  • Centre Hospitalier Régional, Universitaire de Lille 2 Avenue Oscar Lambret, 59000

    Lille

Other trials in France

Sweden1 site

  • Karolinska Institutet and Karolinska University Hospital

    Stockholm

Other trials in Sweden

About this study

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

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:

Read more

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.

Read the detailed description

Indication:

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.

Being tested
Epirubicin, Cisplatin / Oxaliplatin, 5 Flourouracil/ Capecitabine, (41.4 Gy/23 fractions), Paclitaxel
Medical subject headings
Esophageal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EpirubicinDrug

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

  • Cisplatin / OxaliplatinDrug

    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/ CapecitabineDrug

    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)Radiation

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

  • PaclitaxelDrug

    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.

  • CarboplatinDrug

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

  • DocetaxelDrug

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

  • OxaliplatinDrug

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

  • LeucovorinDrug

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

  • 5-FluorouracilDrug

    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

Study groups in NCT01726452
Study groupRoleWhat they receive
A (Modified MAGIC) OR Arm A: FLOTExperimentalModified 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.
Receives: Drug: Epirubicin; Drug: Cisplatin / Oxaliplatin; Drug: 5 Flourouracil/ Capecitabine; Drug: Docetaxel; Drug: Oxaliplatin; Drug: Leucovorin; Drug: 5-Fluorouracil
B (CROSS)ExperimentalArm 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.
Receives: Radiation: (41.4 Gy/23 fractions); Drug: Paclitaxel; Drug: Carboplatin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall survival

    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.

    Measured: At end of trial- up to 3 years in follow up

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Nov 2012 (estimated)
  2. Study start24 Jan 2013
  3. Primary completion4 Aug 2022
  4. Study completion4 Aug 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
377 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01726452
Sponsor's protocol ID
CTRIAL-IE (ICORG) 10-14
Status last verified
Sep 2022
First submitted
6 Nov 2012
Last updated
30 Sep 2022
Results posted
No

Publications

  • 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.

    PubMed 37734399

  • 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.

    PubMed 28578652

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Epirubicin, Cisplatin / Oxaliplatin and 5 Flourouracil/ Capecitabine in people with Adenocarcinoma of the Oesophagus and Adenocarcinoma of the Oesophago-gastric Junction, run by Cancer Trials Ireland at 29 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 29 sites in United Kingdom, Ireland, Denmark, France, Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall survival (time frame: At end of trial- up to 3 years in follow up). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01726452, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Sep 2022.

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