Plain English Summary

Not provided at time of registration

Trial website

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, investigator’s 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

http://www.royalmarsden.nhs.uk/home

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

  1. 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.

  2. 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.

Editorial Notes