Adenocarcinoma of the Oesophagus | NEOadjuvant Trial in Adenocarcinoma of the oEsophagus and oesophagoGastric Junction International Study (Neo-AEGIS)
Adenocarcinoma of the Oesophagus research study
What is the primary objective of this study?
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.
Who is eligible to participate?
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.
Which medical condition, disease, disorder, syndrome, illness, or injury is researched?
Adenocarcinoma of the Oesophagus
Adenocarcinoma of the Oesophago-gastric Junction
Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.
Drug:Epirubicin50mg/m2 on Day 1 of each cycle only (i.e. every 21 days)
Drug:Cisplatin60mg/m2 on day 1 of each cycle only (i.e. every 21 days).
Drug:5 Flourouracil/ Capecitabine5 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).
Radiation:(41.4 Gy/23 fractions)patient will receive 5 weeks of radiation therapy (41.4 Gy/23 fractions).
Drug:Paclitaxel50mg/ 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:CarboplatinDose determined as per calculation,infused on Days 1, 8, 15, 22 and 29.
Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.
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
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.
Start Date: August 2012
Phase: Phase 3
Primary Outcome: Overall survival
Study sponsors, principal investigator, and references
Principal Investigator: John V. Reynolds, Professor
Lead Sponsor: Cancer Trials Ireland
Collaborator: Southampton Clinical Trials Unit