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-DK
• Lead Sponsor: Cancer Trials Ireland

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-12-10
• Last Update Posted: 5 April 2021

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 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 = 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 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 628
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 628

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 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, 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 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.
15. Psychiatric illness/social situations that would limit compliance with study requirements
16. Known Dihydropyrimidine dehydrogenase (DPD) deficiency.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified