A phase II/III randomised trial comparing Epirubicin, Cisplatin and Protracted Venous Infusion (PVI) 5-Fluorouracil (5-FU) (ECF), Epirubicin, Oxaliplatin and PVI 5-FU (EOF), Epirubicin, Cisplatin and Capecitabine (ECX) and Epirubicin, Oxaliplatin and Capecitabine (EOX) in Patients with Advanced Oesophago-Gastric Cancer

ISRCTN	ISRCTN51678883
DOI	https://doi.org/10.1186/ISRCTN51678883
Protocol serial number	MREC 01/2/31
Sponsor	The Royal Marsden NHS Foundation Trust (UK)
Funders	Prof Cunningham's Clinical Research Fund, Roche Pharmaceuticals Research Grant, Sanofi-Aventis Research Grant

Submission date: 15/10/2002
Registration date: 15/10/2002
Last edited: 30/05/2012

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof David Cunningham
Scientific

Royal Marsden Hospital
Downs Road
Sutton, Surrey
SM2 5PT
United Kingdom

Phone	+44 (0)20 8661 3156
Email	david.cunningham@rmh.nhs.uk

Study information

Primary study design	Interventional
Study design	Randomised controlled trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title
Study acronym	The REAL-2 Study
Study objectives	To compare overall and progression free survival in patients treated with these four regimens principally comparing PVI 5FU versus Capecitabine and also Cisplatin versus Oxaliplatin. The aim is to demonstrate non-inferiority between these two main comparisons.
Ethics approval(s)	Not provided at time of registration
Health condition(s) or problem(s) studied	Advanced, oesophageal, oesophago-gastric junctional and gastric cancers.
Intervention	Treatment should commence within 28 days of baseline CT scan and may continue for up to 24 weeks with a maximum of 8 cycles of epirubicin, cisplatin or oxaliplatin. Patients are randomised to receive: 1. ECF Regimen (5-FU, Epirubicin and Cisplatin) 2. EOF Regimen (5-FU, Epirubicin and Oxaliplatin) 3. ECX Regimen (Capecitabine, Epirubicin and Cisplatin) 4. EOX Regimen (Capecitabine, Epirubicin and Oxaliplatin)
Intervention type	Drug
Phase	Phase II/III
Drug / device / biological / vaccine name(s)	Epirubicin, Cisplatin and 5-Fluorouracil (5-FU) (ECF), Epirubicin, Oxaliplatin and 5-FU (EOF), Epirubicin, Cisplatin and Capecitabine (ECX) and Epirubicin, Oxaliplatin and Capecitabine (EOX)
Primary outcome measure(s)	The primary endpoint of the study is overall survival. The study is powered to demonstrate non-inferiority of the 2 x 2 comparisons.
Key secondary outcome measure(s)	1. Response Rates 2.Toxicity 3. Duration of response and progression free survival 4. Quality of life 5. In the phase I part of the study, to establish the optimal dose of capecitabine in the regimens
Completion date	14/11/2005

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	All
Target sample size at registration	1000
Key inclusion criteria	1. Histologically verified locally advanced or metastatic adenocarcinoma, squamous cell carcinoma or undifferentiated carcinoma of the oesophagus, oesophago-gastric junction, or stomach. Patients with positive resection margin or tumour within 1mm of resection margin are eligible. 2. Uni-dimensionally measurable disease, as assessed by computed tomography (CT) and magnetic resonance imaging (MRI) scan in accordance with the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines; evaluable disease, for example on oesophagogastroscopy. The only exception is patients with positive or close resection margins who will be evaluated for survival only. 3. No prior chemotherapy 4. No prior radiotherapy other than adjuvant where relapse is outside the radiotherapy fields 5. A glomerular filtration rate (GFR) of ≥60 ml/min by EDTA clearance or 24 hour urinary creatinine, investigators discretion. Normal serum creatinine. 6. Serum bilirubin <2 x instiutional upper limit of normal range (IULNR) 7. Patients should have a projected life expectancy of at least 3 months 8. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 9. No history of other malignant diseases other than adequately treated non-melanotic skin cancer or in situ carcinoma of the uterine cervix 10. Adequate bone marrow function, white blood cell count (WBC) >3 x 10^9/l, neutrophils >1.5 x 10^9/l, platelets >100 x 10^9/l 11. Written informed consent
Key exclusion criteria	1. Medical or psychiatric condition impairing the ability to give informed consent 2. Uncontrolled angina pectoris, heart failure, clinically significant uncontrolled cardiac arrhythmias, or clinically significant abnormal electrocardiogram (ECG) or cardiac history having a left ventricular ejection fraction (LVEF) of lower limit of normal range for institution as determined by multiple gated acquisition (MUGA) scan or echocardiogram 3. Any other serious uncontrolled medical conditions 4. Any pregnant or lactating woman. Any woman of child bearing potential must have a pregnancy test prior to randomisation and must take adequate precautions to prevent pregnancy during treatment. Any man with a partner of child bearing potential must take adequate precautions to prevent pregnancy during treatment. 5. Inability to complete the quality of life questionnaire
Date of first enrolment	03/03/2000
Date of final enrolment	14/11/2005

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

Royal Marsden Hospital

Sutton, Surrey
SM2 5PT
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	06/06/2005		Yes	No
Results article	results	03/01/2008		Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes