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.|
|ClinicalTrials.gov Identifier: NCT01726452|
Recruitment Status : Recruiting
First Posted : November 15, 2012
Last Update Posted : August 9, 2019
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).
To evaluate one, two and three year survival of patients treated with resection plus neoadjuvant and adjuvant chemotherapy versus resection plus neoadjuvant chemo radiotherapy.
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).
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|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||540 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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|
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.
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.
Docetaxel, 50 mg/m², day 1 of each cycle (i.e. every 14 days)
85 mg/m², day 1 of each cycle (i.e. every 14 days)
200 mg/m², day 1 of each cycle (i.e. every 14 days).
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).
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.
Dose determined as per calculation, infused on Days 1, 8, 15, 22 and 29
- 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.
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 ClinicalTrials.gov identifier (NCT number): NCT01726452
|Contact: Cancer Trials Ireland, Innovation House, Finglas road Dublin 11||+353 1 6677211|
|Contact: Cancer Trials Ireland||+353 1 6677211|
|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|
|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|
|Beaumont Hospital||Active, not recruiting|
|SLRON- St Luke's Radiation Oncology Network||Recruiting|
|Contact: Contact Person +353 1 4065000|
|Principal Investigator: Dr Moya Cunningham|
|St. James's Hospital||Recruiting|
|Contact: Contact Person +353 1 410 3000|
|Principal Investigator: Prof John Reynolds|
|University Hospital Galway||Active, not recruiting|
|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|
|Principal Investigator:||John V. Reynolds, Professor||Trinity Centre, St. James's Hospital, Dublin 8, Ireland|