Try our beta test site
IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2017 by Cancer Trials Ireland
Sponsor:
Collaborators:
Southampton Clinical Trials Unit
Region H Rigshospitalet
Centre Hospitalier Régional, Universitaire de Lille
Information provided by (Responsible Party):
Cancer Trials Ireland
ClinicalTrials.gov Identifier:
NCT01726452
First received: November 6, 2012
Last updated: May 23, 2017
Last verified: May 2017
  Purpose

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

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
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 Regimen) vs. Neoadjuvant Chemoradiation (CROSS Protocol) in Adenocarcinoma of the Oesophagus and Oesophago-gastric Junction

Resource links provided by NLM:


Further study details as provided by Cancer Trials Ireland:

Primary Outcome Measures:
  • 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.


Estimated Enrollment: 366
Study Start Date: August 2012
Estimated Primary Completion Date: January 2024 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A (MAGIC)
MAGIC regimen: Arm A consists of 3 cycles of chemotherapy pre-surgery and a further 3 cycles of chemotherapy post-surgery. Each cycle of chemotherapy lasts 21 days/3 weeks. The drugs used in the MAGIC regimen include Epirubicin, Cisplatin and 5-Flourouracil/ Capecitabine
Drug: Epirubicin
50mg/m2 on Day 1 of each cycle only (i.e. every 21 days)
Drug: Cisplatin
60mg/m2 on day 1 of each cycle only (i.e. every 21 days).
Drug: 5 Flourouracil/ Capecitabine
5 Flourouracil(200 mg/m2/Day)as a continuous intravenous infusion every day for 21 days/3 weeks, Capecitabine (625 mg/m2 twice daily orally)for 21 days/3 weeks. The choice between administering 5 Flourouracil or Capecitabine is at the discretion of the investigator. 5 Flourouracil/ Capecitabine are given daily for the duration of each cycle (i.e. for 9 weeks pre-surgery and for 9 weeks post-surgery).
Experimental: B (CROSS)
Arm B consists of the CROSS protocol, which includes a combination of chemotherapy and radiotherapy prior to surgery. The patient will receive 5 weeks of radiation therapy and 5 weekly cycles of chemotherapy. The radiation will generally commence on the 1st day of treatment and will run for 5 weeks as follows: days 1-5, days 8-12, days 15-19, days 22-26 and days 29-31 inclusive. The chemotherapy and radiotherapy will run concurrently over a 5-week period. Chemotherapy is given by intravenous infusion on days 1, 8, 15, 22 and 29.
Radiation: (41.4 Gy/23 fractions)
patient will receive 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 given IV half an hour before commencing Paclitaxel.Once the Paclitaxel infusion is completed NACL 0.9%,100 ml will be infused IV over half an hour.After this infusion is completed Ondansetron or its equivalent diluted in 100mls NACL 0.9% will be given IV over half an hour on Days 1, 8, 15, 22 and 29.
Drug: Carboplatin
Dose determined as per calculation,infused on Days 1, 8, 15, 22 and 29.

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 MAGIC chemotherapy regimen versus the CROSS neoadjuvant chemo radiation protocol prior to surgery. Patients will be randomised to either Arm A (MAGIC regimen of 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 MAGIC regimen or the CROSS protocol.

Exploratory Study- Translational 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.

  Eligibility

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

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 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01726452

Contacts
Contact: Cancer Trials Ireland, 60 Fitzwilliam Square north, Dublin 2, Ireland +353 1 6677211
Contact: Cancer Trials Ireland +353 1 6677211

Locations
Denmark
Rigshospitalet Recruiting
Blegdamsvej 9, Denmark, 2100 København Ø
Contact: Contact Person    +45 35 45 35 45      
Principal Investigator: Dr Lene Baeksgaard         
France
Centre Hospitalier Régional, Universitaire de Lille 2 Avenue Oscar Lambret, 59000 Not yet recruiting
Lille, France
Contact: Contact Person    +33 3 20 44 41 45      
Principal Investigator: Prof Christophe Mariette         
Ireland
Cork University Hospital Recruiting
Cork, Ireland
Contact: Contact Person    +353 21-4271971      
Principal Investigator: Dr Derek Power         
Beaumont Hospital Recruiting
Dublin, Ireland
Contact: Contact Person    +353 1 809 3000      
Principal Investigator: Prof Liam Grogan         
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 Recruiting
Galway, Ireland
Contact: Contact Person    +353 91 524222      
Principal Investigator: Dr Greg Leonard         
United Kingdom
The Royal Bournemouth Hospital Recruiting
The Royal Bournemouth and Christchurch Hospitals NHS Foundation, Bournemouth, United Kingdom, BH7 7DW
Contact: Contact Person    +44 1202 726127      
Principal Investigator: Joanne Parkinson         
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 Not yet 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 Recruiting
Headington, Oxfordshire, United Kingdom, OX3 7LE
Contact: Contact Person    +44 1865 741841      
Principal Investigator: Somnath Mukherjee         
University Hospital Southampton NHS Foundation Trust Recruiting
Southampton General Hospital, Division A Cancer Care, MP307, T, Southampton, United Kingdom, SO16 6YD
Contact: Contact Person    +44 23 8120 8448      
Principal Investigator: Dr Andrew Bateman         
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         
University Hospitals Bristol NHS Foundation Trust Recruiting
Bristol, United Kingdom, BS2 8ED
Contact: Contact Person    +44 117 342 0231      
Principal Investigator: Dr Stephen Falk         
NHS Lothian, Edinburgh Cancer Centre, Recruiting
Edinburgh, United Kingdom, EH4 2XU
Contact: Contact Person    +44 131 242 3327      
Principal Investigator: Dr Sorcha Campbell         
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         
Sponsors and Collaborators
Cancer Trials Ireland
Southampton Clinical Trials Unit
Region H Rigshospitalet
Centre Hospitalier Régional, Universitaire de Lille
Investigators
Principal Investigator: John V. Reynolds, Professor Trinity Centre, St. James's Hospital, Dublin 8, Ireland
  More Information

Responsible Party: Cancer Trials Ireland
ClinicalTrials.gov Identifier: NCT01726452     History of Changes
Other Study ID Numbers: CTRIAL-IE (ICORG) 10-14
Study First Received: November 6, 2012
Last Updated: May 23, 2017

Additional relevant MeSH terms:
Adenocarcinoma
Esophageal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Cisplatin
Paclitaxel
Albumin-Bound Paclitaxel
Capecitabine
Carboplatin
Epirubicin
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on May 25, 2017