<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01726452</url>
  </required_header>
  <id_info>
    <org_study_id>CTRIAL-IE (ICORG) 10-14</org_study_id>
    <nct_id>NCT01726452</nct_id>
  </id_info>
  <brief_title>NEOadjuvant Trial in Adenocarcinoma of the oEsophagus and oesophagoGastric Junction International Study (Neo-AEGIS)</brief_title>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cancer Trials Ireland</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Southampton Clinical Trials Unit</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Region H Rigshospitalet</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Centre Hospitalier Régional, Universitaire de Lille</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Cancer Trials Ireland</source>
  <brief_summary>
    <textblock>
      This is a multicentre phase III open-labelled, randomised controlled trial. Eligible patients&#xD;
      will be randomised in a 1:1 fashion between neoadjuvant and adjuvant chemotherapy&#xD;
      (Investigator's choice modified MAGIC (ECF/ECX or EOF/EOX) or FLOT regimen) and surgery or&#xD;
      Arm B (CROSS protocol: chemotherapy with radiation therapy and surgery as per multimodal&#xD;
      protocol).&#xD;
&#xD;
      Primary Objective:&#xD;
&#xD;
      To evaluate one, two and three year survival of patients treated with resection plus&#xD;
      neoadjuvant and adjuvant chemotherapy versus resection plus neoadjuvant chemo radiotherapy.&#xD;
&#xD;
      Secondary Objective(s):&#xD;
&#xD;
      To evaluate the effect of both neoadjuvant regimens on clinical and pathological response&#xD;
      rate (in particular relief of dysphagia, improvement in health related quality of life&#xD;
      (HRQL), endoscopic regression, and CT-PET evidence of tumour response), tumour regression&#xD;
      grade, node-positivity, post-operative pathology, disease-free survival, time to treatment&#xD;
      failure, toxicity, post-operative complications and Health Related Quality of Life (HRQL).&#xD;
&#xD;
      Exploratory Objective(s):&#xD;
&#xD;
      Translational Research: The collection of blood and tissue samples for storage in the bio&#xD;
      bank for future research.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Indication:&#xD;
&#xD;
      Patients with cT2-3 N0-1 M0 adenocarcinoma of the oesophagus or junction, based on clinical,&#xD;
      CT-PET, and EUS staging, will be randomised to the modified MAGIC (ECF/ECX or EOF/EOX) or&#xD;
      FLOT regimen and chemotherapy regimen versus the CROSS neoadjuvant chemo radiation protocol&#xD;
      prior to surgery. Patients will be randomised to either Arm A (modified MAGIC or FLOT&#xD;
      chemotherapy only and surgery) or Arm B (CROSS protocol: chemotherapy with radiation therapy&#xD;
      and surgery as per multimodal protocol).&#xD;
&#xD;
      Eligible patients will be randomised in a 1:1 fashion between the modified MAGIC or FLOT&#xD;
      regimen or the CROSS protocol.&#xD;
&#xD;
      Exploratory Study- Translational Research :&#xD;
&#xD;
      The collection of blood and tissue samples for storage in the bio bank for future research.&#xD;
&#xD;
      Patients enrolled in this trial at the St James's' Hospital site, will be invited to consent&#xD;
      to having some of their tissue and blood taken for use in future research studies. Following&#xD;
      consent from the patient, tissue biopsy of tumour and/or normal oesophageal tissue will be&#xD;
      obtained for research at the same time as that biopsied for histological diagnosis. In&#xD;
      addition, tumour and/or normal tissue will also be obtained following surgical resection.&#xD;
      Patient blood samples will also be obtained, both before and during treatment. The&#xD;
      identification of both tumour and circulating biomarkers will increase knowledge of the&#xD;
      molecular mechanism(s) underlying treatment response in oesophageal cancer and may facilitate&#xD;
      the identification of biomarkers predicting patient response to treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 24, 2013</start_date>
  <completion_date type="Actual">August 4, 2022</completion_date>
  <primary_completion_date type="Actual">August 4, 2022</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall survival</measure>
    <time_frame>At end of trial- up to 3 years in follow up</time_frame>
    <description>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.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">377</enrollment>
  <condition>Adenocarcinoma of the Oesophagus</condition>
  <condition>Adenocarcinoma of the Oesophago-gastric Junction</condition>
  <condition>Oesophageal Tumours</condition>
  <condition>Junctional Tumours</condition>
  <condition>Oesophageal Cancer</condition>
  <arm_group>
    <arm_group_label>A (Modified MAGIC) OR Arm A: FLOT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.&#xD;
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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>B (CROSS)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Epirubicin</intervention_name>
    <description>50mg/m2 on Day 1 of each cycle only (i.e. every 21 days)</description>
    <arm_group_label>A (Modified MAGIC) OR Arm A: FLOT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cisplatin / Oxaliplatin</intervention_name>
    <description>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.</description>
    <arm_group_label>A (Modified MAGIC) OR Arm A: FLOT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>5 Flourouracil/ Capecitabine</intervention_name>
    <description>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.</description>
    <arm_group_label>A (Modified MAGIC) OR Arm A: FLOT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>(41.4 Gy/23 fractions)</intervention_name>
    <description>Patient will receive 4.5 weeks of radiation therapy (41.4 Gy/23 fractions).</description>
    <arm_group_label>B (CROSS)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Paclitaxel</intervention_name>
    <description>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.</description>
    <arm_group_label>B (CROSS)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carboplatin</intervention_name>
    <description>Dose determined as per calculation, infused on Days 1, 8, 15, 22 and 29</description>
    <arm_group_label>B (CROSS)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Docetaxel</intervention_name>
    <description>Docetaxel, 50 mg/m², day 1 of each cycle (i.e. every 14 days)</description>
    <arm_group_label>A (Modified MAGIC) OR Arm A: FLOT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxaliplatin</intervention_name>
    <description>85 mg/m², day 1 of each cycle (i.e. every 14 days)</description>
    <arm_group_label>A (Modified MAGIC) OR Arm A: FLOT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Leucovorin</intervention_name>
    <description>200 mg/m², day 1 of each cycle (i.e. every 14 days).</description>
    <arm_group_label>A (Modified MAGIC) OR Arm A: FLOT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>5-Fluorouracil</intervention_name>
    <description>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</description>
    <arm_group_label>A (Modified MAGIC) OR Arm A: FLOT</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Histologically verified adenocarcinoma of the oesophagus or oesophago-gastric junction&#xD;
             based on endoscopy (OGD)&#xD;
&#xD;
          2. CT-18FDG-PET performed in all patients for disease staging.&#xD;
&#xD;
          3. EUS in all patients unless luminal obstruction precludes sensitivity of the test.&#xD;
&#xD;
          4. Staging laparoscopy performed at the investigator's discretion for locally advanced&#xD;
             AEG II and AEG III tumours .&#xD;
&#xD;
          5. Pre-treatment stage cT2-3, N0-3, M0.&#xD;
&#xD;
          6. Maximum tumour length should be no more than 8cm (equal to 8 cm is acceptable)&#xD;
&#xD;
          7. Male/female patients aged ≥18 years&#xD;
&#xD;
          8. ECOG Performance Status 0, 1 or 2 (Appendix F).&#xD;
&#xD;
          9. ASA I-II (Appendix F).&#xD;
&#xD;
         10. Adequate cardiac function. For all patients, an ejection fraction of &gt; 50% is&#xD;
             required. If patients have a known cardiac history (e.g. known ischemic disease,&#xD;
             cardiomyopathy) an ejection fraction &gt; 50% and cardiac clearance by a consultant&#xD;
             cardiologist for major surgery and cancer therapies is required.&#xD;
&#xD;
         11. Adequate respiratory function. Patients should have pulmonary function tests completed&#xD;
             with a minimum FEV1 ≥ 1.5L. CPEX acceptable&#xD;
&#xD;
         12. Adequate bone marrow function: absolute neutrophil count (ANC) &gt;1.5x109/l; white blood&#xD;
             cell count &gt;3x109/l; platelets &gt;100x109/l; haemoglobin (Hb) &gt;9g/dl (can be&#xD;
             post-transfusion).&#xD;
&#xD;
         13. Adequate renal function: glomerular filtration rate &gt;60ml/minute calculated using the&#xD;
             Cockcroft-Gault Formula (Appendix O).&#xD;
&#xD;
         14. Adequate liver function: serum bilirubin &lt;1.5x ULN; AST &lt;2.5x ULN and ALP &lt;3x ULN (ULN&#xD;
             as per institutional standard).&#xD;
&#xD;
         15. Written informed consent must be obtained from the patient before any study-trial&#xD;
             specific procedures are performed.&#xD;
&#xD;
         16. Women of child-bearing potential and male subjects must agree to use an effective&#xD;
             barrier method of contraception for up to 6 months following discontinuation of&#xD;
             therapy. Effective contraception is defined as any medically recommended (or&#xD;
             combination of methods) as per standard of care.&#xD;
&#xD;
         17. Women of childbearing potential must have pregnancy excluded by urine or serum&#xD;
             beta-HCG testing within 7 days prior to treatment.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Tumours of squamous histology.&#xD;
&#xD;
          2. Patients with advanced inoperable or metastatic oesophageal, junctional or gastric&#xD;
             adenocarcinoma.&#xD;
&#xD;
          3. Disease length (total length of tumour plus node) greater than 10cm (up to 10 cm will&#xD;
             be allowed) -as measured by any modality or, if appropriate, combination of&#xD;
             modalities-, unless in the opinion of the investigator in discussion with national RT&#xD;
             lead, it is felt that OAR constraints are likely to be achievable.&#xD;
&#xD;
          4. Any prior chemotherapy for gastrointestinal cancer.&#xD;
&#xD;
          5. Prior abdominal or thoracic, chest wall or breast radiotherapy.&#xD;
&#xD;
          6. Patients who are unfit for surgery or cancer treatments based on cardiac disease.&#xD;
&#xD;
          7. Patients with acute systemic infections.&#xD;
&#xD;
          8. Patients who are receiving treatment with sorivudine or its chemical related&#xD;
             analogues, such as brivudine which is contraindicated with capecitabine and&#xD;
             5-fluorouracil administration.&#xD;
&#xD;
          9. Clinical COPD with significant obstructive airways disease classified by FEV1 &lt; 1.5 L&#xD;
             or PaO2 less than 9kPa on room air&#xD;
&#xD;
         10. Known peripheral neuropathy &gt;Grade 1 (absence of deep tendon reflexes as the sole&#xD;
             neurological abnormality does not render the patient ineligible).&#xD;
&#xD;
         11. Known positive tests for human immunodeficiency virus (HIV) infection, acute or&#xD;
             chronic active hepatitis B infection.&#xD;
&#xD;
         12. Any other malignancies within the last 5 years (other than curatively treated basal&#xD;
             cell carcinoma of the skin and/or in situ carcinoma of the cervix)&#xD;
&#xD;
         13. Participation in other clinical trials of investigational or marketed agents for the&#xD;
             treatment of oesophageal cancer or other diseases within 30 days from registration. UK&#xD;
             sites please refer to Group Specific Appendix&#xD;
&#xD;
         14. Women who are pregnant or breastfeeding.&#xD;
&#xD;
         15. Psychiatric illness/social situations that would limit compliance with study&#xD;
             requirements.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>John V. Reynolds, Professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Trinity Centre, St. James's Hospital, Dublin 8, Ireland</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Rigshospitalet</name>
      <address>
        <city>Blegdamsvej 9</city>
        <zip>2100 København Ø</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Régional, Universitaire de Lille 2 Avenue Oscar Lambret, 59000</name>
      <address>
        <city>Lille</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cork University Hospital</name>
      <address>
        <city>Cork</city>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beaumont Hospital</name>
      <address>
        <city>Dublin</city>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SLRON- St Luke's Radiation Oncology Network</name>
      <address>
        <city>Dublin</city>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. James's Hospital</name>
      <address>
        <city>Dublin</city>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Galway</name>
      <address>
        <city>Galway</city>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Karolinska Institutet and Karolinska University Hospital</name>
      <address>
        <city>Stockholm</city>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Royal Bournemouth Hospital</name>
      <address>
        <city>The Royal Bournemouth And Christchurch Hospitals NHS Foundation</city>
        <state>Bournemouth</state>
        <zip>BH7 7DW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cambridge University Hospitals NHS Foundation Trust</name>
      <address>
        <city>Addenbrooke's Hospital, Box 279(s4), Cambridge Biomedical Camp</city>
        <state>Cambridge</state>
        <zip>CB2 0QQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Velindre Cancer Centre</name>
      <address>
        <city>Velindre NHS Trust, Velindre Road, Whitchurch</city>
        <state>Cardiff</state>
        <zip>CF14 2TL</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospitals Coventry &amp; Warwickshire</name>
      <address>
        <city>Clifford Bridge Road, Walsgrave</city>
        <state>Coventry</state>
        <zip>CV2 2DX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hull and East Yorkshire Hospitals NHS Trust, Castle Hill Hospital,</name>
      <address>
        <city>Cottingham</city>
        <state>East Riding Of Yorkshire</state>
        <zip>HU16 5JQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Portsmouth Hospitals NHS Trust</name>
      <address>
        <city>Southwick Hill Road, Cosham</city>
        <state>Hampshire</state>
        <zip>PO6 3LY</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mount Vernon Cancer Centre</name>
      <address>
        <city>E &amp; N Hertfordshire NHS Trust, Rickmansworth Road, Northwood</city>
        <state>Middlesex</state>
        <zip>HA6 2RN</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nottingham City Hospital</name>
      <address>
        <city>Nottingham University Hospitals NHS Trust, Hucknall Road</city>
        <state>Nottingham</state>
        <zip>HG5 1PB</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oxford University Hospital NHS Trust Churchill Hospital</name>
      <address>
        <city>Headington</city>
        <state>Oxfordshire</state>
        <zip>OX3 7LE</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Southampton NHS Foundation Trust</name>
      <address>
        <city>Southampton General Hospital, Division A Cancer Care, Mp307, T</city>
        <state>Southampton</state>
        <zip>SO16 6YD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Surrey County Hospital</name>
      <address>
        <city>Guildford</city>
        <state>Surrey</state>
        <zip>GU2 7XX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Worcestershire Royal Hospital</name>
      <address>
        <city>Worcestershire Oncology Centre, Charles Hastings Way</city>
        <state>Worcester</state>
        <zip>WR5 1DD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Belfast Health and Social Care Trust, Northern Ireland Cancer Centre, Belfast CityHospital</name>
      <address>
        <city>Belfast</city>
        <zip>BT9 7AB</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Clatterbridge Cancer Centre NHS Foundation Trust</name>
      <address>
        <city>Birkenhead, Wirral</city>
        <zip>CH63 4JY</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospitals Bristol NHS Foundation Trust</name>
      <address>
        <city>Bristol</city>
        <zip>BS2 8ED</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Plymouth NHS Trust</name>
      <address>
        <city>Derriford Hospital, Derriford Road, Crownhill, Plymouth</city>
        <zip>PL6 8DH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NHS Lothian, Edinburgh Cancer Centre,</name>
      <address>
        <city>Edinburgh</city>
        <zip>EH4 2XU</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beatson West of Scotland Cancer Centre</name>
      <address>
        <city>Glasgow, 1056 Great Western Road</city>
        <zip>G12 0YN</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Imperial College Healthcare NHS Trust St Mary's Hospital</name>
      <address>
        <city>London</city>
        <zip>W2 1NY</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Newcastle upon Tyne Hospital NHS Foundation TrustFreeman Hospital, Freeman Road, High Heaton</name>
      <address>
        <city>Newcastle upon Tyne</city>
        <zip>NE7 7DN</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Preston Hospital</name>
      <address>
        <city>Sharoe Garoo Lane, Fulwood, Preston</city>
        <zip>PR2</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
    <country>France</country>
    <country>Ireland</country>
    <country>Sweden</country>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>November 6, 2012</study_first_submitted>
  <study_first_submitted_qc>November 9, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 15, 2012</study_first_posted>
  <last_update_submitted>September 29, 2022</last_update_submitted>
  <last_update_submitted_qc>September 29, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 30, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adenocarcinoma</mesh_term>
    <mesh_term>Esophageal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leucovorin</mesh_term>
    <mesh_term>Paclitaxel</mesh_term>
    <mesh_term>Docetaxel</mesh_term>
    <mesh_term>Carboplatin</mesh_term>
    <mesh_term>Fluorouracil</mesh_term>
    <mesh_term>Capecitabine</mesh_term>
    <mesh_term>Oxaliplatin</mesh_term>
    <mesh_term>Epirubicin</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01726452
org study id: CTRIAL-IE (ICORG) 10-14
nct id: NCT01726452
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall survival
time frame: At end of trial- up to 3 years in follow up
description: 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.
arm group label: A (Modified MAGIC) OR Arm A: FLOT
arm group type: Experimental
description: 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.
arm group label: B (CROSS)
arm group type: Experimental
description: 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.
intervention type: Drug
intervention name: Epirubicin
description: 50mg/m2 on Day 1 of each cycle only (i.e. every 21 days)
arm group label: A (Modified MAGIC) OR Arm A: FLOT
intervention type: Drug
intervention name: Cisplatin / Oxaliplatin
description: 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.
arm group label: A (Modified MAGIC) OR Arm A: FLOT
intervention type: Drug
intervention name: 5 Flourouracil/ Capecitabine
description: 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.
arm group label: A (Modified MAGIC) OR Arm A: FLOT
intervention type: Radiation
intervention name: (41.4 Gy/23 fractions)
description: Patient will receive 4.5 weeks of radiation therapy (41.4 Gy/23 fractions).
arm group label: B (CROSS)
intervention type: Drug
intervention name: Paclitaxel
description: 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.
arm group label: B (CROSS)
intervention type: Drug
intervention name: Carboplatin
description: Dose determined as per calculation, infused on Days 1, 8, 15, 22 and 29
arm group label: B (CROSS)
intervention type: Drug
intervention name: Docetaxel
description: Docetaxel, 50 mg/m², day 1 of each cycle (i.e. every 14 days)
arm group label: A (Modified MAGIC) OR Arm A: FLOT
intervention type: Drug
intervention name: Oxaliplatin
description: 85 mg/m², day 1 of each cycle (i.e. every 14 days)
arm group label: A (Modified MAGIC) OR Arm A: FLOT
intervention type: Drug
intervention name: Leucovorin
description: 200 mg/m², day 1 of each cycle (i.e. every 14 days).
arm group label: A (Modified MAGIC) OR Arm A: FLOT
intervention type: Drug
intervention name: 5-Fluorouracil
description: 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
arm group label: A (Modified MAGIC) OR Arm A: FLOT
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: John V. Reynolds, Professor
role: Principal Investigator
affiliation: Trinity Centre, St. James's Hospital, Dublin 8, Ireland
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country: Denmark
country: France
country: Ireland
country: Sweden
country: United Kingdom
responsible party type: Sponsor
mesh term: Adenocarcinoma
mesh term: Esophageal Neoplasms
mesh term: Leucovorin
mesh term: Paclitaxel
mesh term: Docetaxel
mesh term: Carboplatin
mesh term: Fluorouracil
mesh term: Capecitabine
mesh term: Oxaliplatin
mesh term: Epirubicin