ESPAC-4

Title

EUROPEAN STUDY GROUP FOR PANCREATIC CANCER (ESPAC) -Trial 4. Combination versus single agent adjuvant chemotherapy in resectable pancreatic cancer.

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
III	Treatment	Open	Over 18	University of Liverpool and RLBUHT	EUDRACT No: 2007-004299-38 ISRCTN No: 96397434

Trial Description

Purpose

Long term survival following resection for pancreatic cancer still needs to be improved. Adjuvant 5-FU/FA demonstrates significant improvement in overall survival following surgery, adjuvant gemcitabine demonstrates a survival advantage following surgical resection for pancreatic cancer. Gemcitabine plus capecitabine improves survival in patients with advanced pancreatic cancer compared with single agent gemcitabine

Eligibility

Inclusion Criteria:

Patients who have undergone complete macroscopic resction for ductal adenocarcinoma of the pancreas (R0 or R1 resection).
Completion of all pre-operative investigations.
Histological confirmation of the primary diagnosis.
Histological examination of all resection margins.
Patients randomised within 12 weeks of surgery and can begin treatment within 14 weeks.
No evidence of malignant ascites, liver metastasis, spread to other distant abdominal organs, peritoneal metastasis, spread to extra-abdominal organs – CT (chest, abdomen, pelvis) scan within 3 months prior to randomisation.
A WHO performance status < 2
Creatinine clearance = 50ml/min (according to Cockcroft and Gault)
Fully recovered from the operation and fit to take part in the trial.
Able to attend for administration of the adjuvant therapy.
Able to attend for long-term follow-up.
Life expectancy > 3 months.
No previous or concurrent malignancy diagnoses (except curatively-treated basal cell carcinoma of skin, carcinoma in situ of cervix).
No serious medical or psychological condition precluding adjuvant treatment.
Fully informed written consent given.

Exclusion Criteria:

Use of neo-adjuvant chemotherapy or other concomitant chemotherapy.
Patients with pancreatic lymphoma.
Macroscopically remaining tumour (R2 resection).
Patients with TNM Stage IV disease.
Patients younger than 18 years.
Pregnancy.
New York Heart Association Classification Grade III or IV.
Previous chemotherapy.
All men or women of reproductive potential, unless using at least two contraceptive precautions, one of which must be a condom.
Patients with known malabsorption.
Patients with neutrophil counts of <1.5 x 109/l.
Patients with thrombocyte counts of <100 x 109/l.
Patients with severe hepatic impairment.

Treatment/Intervention

ESPAC-4 is a phase III, international, randomised controlled trial which aims to compare gemcitabine against gemcitabine + capecitabine in 1080 patients with ductal adenocarcinoma. It is anticipated that the trial will run in approximately 160 sites within 18 countries and will run for 8 years.

The study will randomise patients into one of two arms up to 10 weeks following pancreatic cancer resection surgery. The two treatment arms will be gemcitabine plus capecitabine versus gemcitabine. If one treatment shows superiority in terms of the primary and secondary endpoints, this could be recommended as a standard treatment in the UK.

Arm 1: Gemcitabine will be administered once a week for three weeks out of every four weeks (one cycle) for six cycles i.e. 24 weeks. Arm 2: Gemcitabine will be administered on day 1, 8 and 15. Capecitabine will be administered orally for 21 days followed by 7 days? rest. Treatment will be repeated every 4 weeks for a total of 24 weeks

Trial Endpoints

Primary Outcome

Length of survival

Secondary outcomes

Toxicity
Quality of life
Two year survival
Five year survival
Relapse free survival (RFS)

Trial Lead Organisations

The Royal Liverpool and Broadgreen University Hospital Trust
University of Liverpool
Chief Investigator: Professor John Neoptolemos

Trial Sites

There are now 37 sites open in the trial:

Addenbrooke's Hospital, Cambridge (Dr. Pippa Corrie)
Basingstoke and North Hampshire Hospital, Basingstoke (Dr. Charlotte Rees)
Bradford Royal Infirmary, Bradford (Dr. Sue Cheeseman)
Bristol Haematology and Oncology Centre, Bristol (Dr. Stephen Falk)
Clatterbridge Centre for Oncology, Wirral (Dr. David Smith)
Cumberland Infirmary, Carlisle (Dr. Jonathan Nicoll)
Derriford Hospital, Plymouth (Dr. Sarah Pascoe)
Eskilstuna, S-631 88 Eskilstuna (Prof. Pehr Lind)
Guy's Hospital, London (Dr. Paul Ross)
Ipswich Hospital, Ipswich (Dr. Rubin Soomal)
Karolinska University Hospital, Stockholm (Prof. Pehr Lind)
Linkoping, Linköping ( Johan Haux)
Lund, Lund ( Anders Johnsson)
Malmo, 205 02 Malmö ( Lianna Kadar)
Newcastle General Hospital, Newcastle upon Tyne (Dr. Kate Sumpter)
Norfolk and Norwich University Hospital, Norwich (Dr. Tom Roques)
North Devon District Hospital, Barnstaple (Dr. Mark Napier)
Nottingham City Hospital, Nottingham (Prof. Srinivasan Madhusudan)
Peterborough District Hospital, Peterborough (Dr. Karen McAdam)
Poole General Hospital, Poole (Dr. Richard Osborne)
Royal Bournemouth Hospital, Bournemouth (Dr. Tamas Hickish)
Royal Derby Hospital, Derby (Dr. Rengarajan Vijayan)
Royal Free Hospital, London (Dr. Tim Meyer)
Royal Liverpool University Hospital, Liverpool (Dr. David Smith)
Royal Marsden Hospital, London (Prof. David Cunningham)
Royal Surrey County Hospital, Guildford (Dr. Gary Middleton)
Salisbury District Hospital, Salisbury (Dr. Tim J Iveson)
Southampton General Hospital, Southampton (Dr. Tim J Iveson)
St James's University Hospital, Leeds (Dr. Alan Anthoney)
Sundsvall, Sundsvall ( Petra Flygare)
The Christie, Manchester (Dr. Juan Valle)
Umea University Hospital, ( Ingegerd Karlberg)
University Hospital Walsgrave, Coventry (Dr. Sharmila Sothi)
Uppsala University Hospital, (Prof. Bengt Glimelius)
Västerås, Västerås ( Henry Letocha)
Weston Park Hospital, Sheffield (Dr. Jonathan C Wadsley)
Yeovil District Hospital, Yeovil (Dr. Julie Walther)

The following sites have expressed an interest:

Aberdeen Royal Infirmary, Aberdeen (Dr. Marianne Nicolson)
Airedale General Hospital, Keighley (Dr. Sue Cheeseman)
Alexandra Hospital, Redditch (Dr. Sharmila Sothi)
Beatson Oncology Centre, Glasgow (Dr. Alec McDonald)
Belfast City Hospital, Belfast (Dr. Martin Eatock)
Castle Hill Hospital, Cottingham (Dr. Anthony Maraveyas)
Churchill Hospital, Oxford (Dr. Kinnari Patel)
Darent Valley Hospital, Dartford (Dr. Riyaz Shah)
Ernst-Moritz-Arndt Universitat Greifswald, D - 17487 Greifswald (Prof. Markus Lerch)
Glan Clwyd Hospital, Rhyl (Dr. Angel Garcia)
Goteborg, Göteborg ( Tor Ekman)
Hammersmith Hospital, London (Dr. Harpreet Wasan)
Hinchingbrooke Hospital, Huntingdon (Dr. Cheryl Palmer)
Huddersfield Royal Infirmary, Huddersfield (Dr. Jo Dent)
James Paget Hospital, Great Yarmouth (Dr. Ulrike Dernedde)
Kent and Canterbury Hospital, Canterbury (Dr. Justin Waters)
Kent Oncology Centre, Maidstone (Dr. Mark Hill)
Kings College Hospital, London (Dr. Paul Ross)
Klinikum Rechts Der Isar Der Tu Munchen, D-81675 Munchen (Prof. Helmut Friess)
Leicester Royal Infirmary, Leicester (Prof. Will Steward)
Manchester Royal Infirmary, Manchester (Prof Ajith Kumar Siriwardena)
Morriston Hospital, Swansea ( Bilal Al-Sarireh)
North Manchester General Hospital, Manchester (Dr. Juan Valle)
North Middlesex Hospital, London (Dr. John Bridgewater)
North Staffordshire Royal Infirmary, Stoke-on-Trent (Dr. Fawzi Adab)
Orebro, Örebro ( Mattias Elmlund)
Queen Elizabeth Hospital, Birmingham (Dr. Daniel Palmer)
Queens Hospital, Romford, Romford (Dr. Sherif Raouf)
Raigmore Hospital, Inverness (Dr. David Whillis)
Royal Blackburn Hospital, Blackburn (Mr David Chang)
Royal Devon & Exeter Hospital, Exeter (Dr. Elizabeth Toy)
Singleton Hospital, Swansea (Dr. Colin Askill)
Southend Hospital, Westcliff-on-Sea (Dr. Pauline Leonard)
St Bartholomew's Hospital, London (Dr. Sarah Slater)
St Josef Hospital Bochum, 44791 Bochum ( Uhl Waldemar)
Tayside Cancer Centre, Dundee (Dr. Douglas Adamson)
The Great Western Hospital, Swindon (Dr. Claire Blesing)
Torbay Hospital, Torquay (Dr. Nicole Dorey)
Uke Hamburg, Hamburg (Prof. Dr. Med. Jakob R. Izbicki)
Universitatsklinik Leipzig, Leipzig ( Joachim Mössner)
University College Hospital, London (Dr. John Bridgewater)
University Hospital of North Durham, Durham (Dr. Fareeda Coxon)
University Of Heidelberg, 61920 Heidelberg (Prof. Markus Büchler)
Velindre Hospital, Cardiff (Dr. Tom Crosby)
Wansbeck General Hospital, Ashington (Dr. Paula Mulvenna)
Western General Hospital, Edinburgh (Dr. Lucy Wall)
Wrexham Maelor Hospital, Wrexham (Dr. Simon Gollins)

Registry Information

Official Title