Randomised Clinical Trial of neoadjuvant and adjuvant chemotherapy(Investigator’s choice Modified MAGIC or FLOT regimen) vs. neoadjuvant chemoradiation (CROSS protocol) in adenocarcinoma of the oesophagus and oesophago-gastric junctio

Phase 1

Conditions: Adenocarcinoma of the oesophagus and oesophagastric junction
MedDRA version: 21.1Level: LLTClassification code 10066354Term: Adenocarcinoma of the gastroesophageal junctionSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 21.0Level: PTClassification code 10030137Term: Oesophageal adenocarcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2011-001858-28-SE

Lead Sponsor: Cancer Trials Ireland

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 540

Inclusion Criteria

Countries with Group Specific Appendices with sections relating to the inclusion and exclusion criteria, should refer to this documents when reviewing patient eligibility.

1. Histologically verified adenocarcinoma of the oesophagus, or oesophago-gastric junction based on OGD.
2. CT- 18FDG-PET performed in all patients for disease staging
3. Staging laparoscopy will be performed at the investigator’s discretion for locally advanced AEG II and AEG III tumours.
4. Pre-treatment stage cT2-3, N0-3, M0.
5. Maximum tumour length should be no more than 8cm (equal to 8 cm is acceptable).
6. Male/female patients aged =18 years.
7. ECOG Performance Status 0, 1 or 2 (Appendix D).
8. ASA Grading I-II (Appendix D).
9. Adequate cardiac function. In the opinion of the treating Investigator the patient has adequate cardiac function for major surgery and cancer therapies. For patients with a known cardiac history (e.g. known ischemic disease, cardiomyopathy) or cardiac symptoms an ejection fraction > 50% is required.
10. Adequate respiratory function. Patients should have pulmonary function tests completed with a minimum FEV1=1.5L. CPEX acceptable.
11. 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).
12. Adequate renal function: glomerular filtration rate > 60ml/minute calculated using the Cockcroft-Gault Formula (Appendix M).
13. Adequate liver function: serum bilirubin = ULN; AST <2.5x ULN and ALP <3x ULN (ULN as per institutional standard).
14. Written informed consent must be obtained from the patient before any study-specific procedures are performed.
15. 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 barrier method of contraception is defined as any medically recommended (or combination of methods) as per standard of care.
16. Women of child bearing potential must have pregnancy excluded by urine or serum beta-HCG testing within 7 calendar days prior to registration.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 270
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 270

Exclusion Criteria

Countries with Group Specific Appendices with sections relating to the inclusion and exclusion criteria, should refer to this documents when reviewing patient eligibility.
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 10 cm (up to 10 cm will be allowed) -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 Organ At Risk (OAR) constraints are likely to be achievable.
4. Any prior chemotherapy for gastrointestinal cancer.
5. Prior abdominal, thoracic, chest wall or breast 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 Chronic Obstructive Pulmonary Disease (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 prior to registration. UK sites please refer to Group Specific Appendix.
14. Women who are pregnant or breastfeeding.
15. Psychiatric illness/social situations that would limit compliance with study requirements.
16. Known Dihydropyrimidine hydrogenase (DPD) deficiency.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

Related Trials