Contact information
Type
Scientific
Primary contact
Prof David Cunningham
ORCID ID
Contact details
Royal Marsden Hospital
Downs Road
Sutton
Surrey
SM2 5PT
United Kingdom
+44 (0)20 8661 3156
david.cunningham@rmh.nhs.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
MREC 01/2/31
Study information
Scientific title
Acronym
The REAL-2 Study
Study hypothesis
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
Not provided at time of registration
Study design
Randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
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 names
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 measures
The primary endpoint of the study is overall survival. The study is powered to demonstrate non-inferiority of the 2 x 2 comparisons.
Secondary outcome measures
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
Overall trial start date
03/03/2000
Overall trial end date
14/11/2005
Reason abandoned
Eligibility
Participant 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
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
1000
Participant 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
Recruitment start date
03/03/2000
Recruitment end date
14/11/2005
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Royal Marsden Hospital
Sutton, Surrey
SM2 5PT
United Kingdom
Sponsor information
Organisation
The Royal Marsden NHS Foundation Trust (UK)
Sponsor details
Downs Road
Sutton
SM2 5PT
United Kingdom
+44 (0)20 8661 3156
Sponsor type
Not defined
Website
Funders
Funder type
Industry
Funder name
Prof Cunningham's Clinical Research Fund
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Roche Pharmaceuticals Research Grant
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Sanofi-Aventis Research Grant
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary
1. 2005 results in http://www.ncbi.nlm.nih.gov/pubmed/15928658
2. 2008 results in http://www.ncbi.nlm.nih.gov/pubmed/18172173
Publication citations
-
Results
Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, Middleton G, Daniel F, Oates J, Norman AR, , Capecitabine and oxaliplatin for advanced esophagogastric cancer., N. Engl. J. Med., 2008, 358, 1, 36-46, doi: 10.1056/NEJMoa073149.
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Sumpter K, Harper-Wynne C, Cunningham D, Rao S, Tebbutt N, Norman AR, Ward C, Iveson T, Nicolson M, Hickish T, Hill M, Oates J, Report of two protocol planned interim analyses in a randomised multicentre phase III study comparing capecitabine with fluorouracil and oxaliplatin with cisplatin in patients with advanced oesophagogastric cancer receiving ECF., Br. J. Cancer, 2005, 92, 11, 1976-1983, doi: 10.1038/sj.bjc.6602572.