MAGIC vs. CROSS Upper GI. ICORG 10-14, V3
Conditions
Adenocarcinoma of the Oesophagus - Adenocarcinoma of the Oesophago-gastric Junction - Oesophageal Tumours - Junctional Tumours - Oesophageal Cancer
Conditions: official terms
Adenocarcinoma - Esophageal Neoplasms
Study Type
Interventional
Study Phase
Phase 3
Study Design
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: Epirubicin Type: Drug
Name: Cisplatin Type: Drug
Name: 5 Flourouracil/ Capecitabine Type: Drug
Name: (41.4 Gy/23 fractions) Type: Radiation
Name: Paclitaxel Type: Drug
Name: Carboplatin Type: Drug
Overall Status
Recruiting
Summary
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.
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 :

All patients enrolled in this trial, 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.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
Criteria: Inclusion Criteria:

1. Histologically verified adenocarcinoma of the oesophagus or oesophago-gastric junction.

2. CT- 18FDG-PET and EUS in all patients

3. Staging laparoscopy will be performed for tumours of the abdominal oesophagus, junction and proximal stomach i.e. AEG II and AEG III (at the investigators discretion)

4. Pre-treatment stage cT2-3, N0-1, M0

5. No prior abdominal or thoracic radiotherapy

6. Male/female patients aged >18 years.

7. WHO Performance Status 0, 1 or 2

8. ASA I-II

9. Completion of baseline quality of life questionnaire (EORTC QLQ C30).

10. Adequate cardiac function. Patients with a cardiac history should have a cardiology review and should have a left ventricular ejection fraction > 50% (as determined by MUGA scan or ECHO).

11. Adequate respiratory function. Patients should have pulmonary function tests completed with FEV1 > 1.5L

12. Adequate bone marrow function: absolute neutrophil count (ANC) >1.5x10^9/l; white blood cell count >3x10^9/l; platelets >100x10^9/l; haemoglobin (Hb) >9g/dl (can be post-transfusion).

13. Adequate renal function: glomerular filtration rate >60ml/minute (calculated or measured).

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.

Exclusion Criteria:

1. Tumours of squamous histology.

2. Patients with advanced inoperable or metastatic oesophageal, junctional or gastric adenocarcinoma.

3. Any prior chemotherapy for gastrointestinal cancer.

4. Prior abdominal or thoracic radiation.

5. Clinically significant (i.e. active) cardiac disease (e.g. symptomatic coronary artery disease or myocardial infarction within the last 12 months. Patients with any history of clinically significant cardiac failure are excluded from study entry.

6. Clinical COPD with significant obstructive airways disease classified by FEV1 < 1.5 L or PaO2 less than 9kPa on room air

7. Known peripheral neuropathy >Grade 1 (absence of deep tendon reflexes as the sole neurological abnormality does not render the patient ineligible).

8. Known positive tests for human immunodeficiency virus (HIV) infection, , acute or chronic active hepatitis B infection.

9. 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)
Locations
Cork Mercy / CUH
Cork, Ireland
Status: Recruiting
Contact: Contact Person - 021-4935362
Cork University Hospital
Cork, Ireland
Status: Not yet recruiting
Contact: Contact person - 021-4271971
Beaumont Hospital
Dublin, Ireland
Status: Recruiting
Contact: Contact person - (01) 809 3000
SLRON- St Luke's Radiation Oncology Network
Dublin, Ireland
Status: Recruiting
Contact: Contact person - 01 4065000
St. James's Hospital
Dublin, Ireland
Status: Recruiting
Contact: Contact person - 01 410 3000
Galway University Hospital
Galway, Ireland
Status: Not yet recruiting
Contact: Contact person - (0)91 524222
Start Date
August 2012
Sponsors
ICORG- All Ireland Cooperative Oncology Research Group
Source
ICORG- All Ireland Cooperative Oncology Research Group
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page