Condition category
Date applied
Date assigned
Last edited
Prospectively registered
Overall trial status
Recruitment status
No longer recruiting

Contact information



Primary contact

Prof John Neoptolemos


Contact details

University of Liverpool
Division of Surgery and Oncology
The Duncan Building
Daulby Street
L69 3GA
United Kingdom



Additional contact

Dr Karl Harvey


Contact details

University of Liverpool
Division of Surgery and Oncology
The Duncan Building
Daulby Street
L69 3GA
United Kingdom

Additional identifiers

EudraCT number

2007-004299-38 number

Protocol/serial number


Study information

Scientific title

European Study Group for Pancreatic Cancer (ESPAC) - Trial 4: combination versus single agent adjuvant chemotherapy in resectable pancreatic cancer



Study hypothesis

To investigate if combination chemotherapy (gemcitabine and capecitabine), when used as adjuvant therapy in patients following resection for pancreatic adenocarcinoma, improves survival over adjuvant therapy using gemcitabine alone.

Ethics approval

1. Liverpool Adult Research Multi-centre Research Ethics Committee (MREC), 04/03/2008, ref: 08/H1005/1
2. MHRA acceptance also received on 20/02/2008, ref: 04196/0009/001

Study design

Phase III international randomised controlled trial

Primary study design


Secondary study design

Randomised controlled trial

Trial setting


Trial type


Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet


Resectable pancreatic cancer


Gemcitabine and capecitabine versus gemcitabine alone

Gemcitabine administration:
1,000 mg/m^2 gemcitabine must be given as an intravenous infusion, the lyophilised powder being diluted in normal saline, over 30 minutes unless haematological toxicity occurs requiring dose adjustment. Administer on day 1, 8 and 15 (one cycle) for six cycles i.e. 24 weeks.

Capecitabine administration:
830 mg/m^2 capecitabine must be administered orally morning and evening daily (total daily dose of 1,660 mg/m^2) unless toxicity occurs requiring dose adjustment. The gemcitabine and capecitabine combination schedule used in this study originates from phase I data published by Schilsky et al. In this study the maximum tolerated dose was defined at gemcitabine 1 g/m^2 on days 1, 8 and 15, and capecitabine 1,660 mg/m^2/day given on days 1 - 21 every 28 days.

Intervention type



Phase III

Drug names

Gemcitabine, capecitabine

Primary outcome measure

Current primary outcome measure as of 31/05/2011:
Length of survival. Duration of follow-up: 60 months from randomisation.

Previous primary outcome measure:
Length of survival. Duration of follow-up: 60 months from the date of surgery.

Secondary outcome measures

1. Toxicity. Duration of follow-up: 60 months from the date of surgery.
2. Quality of life, assessed by the European Organisation for Research and Treatment of Cancer, Quality of Life Questionnaires (EORTC C-30 QLQ) at baseline, 3, 6, 12, 16 and 24 months and annually thereafter up to 60 months
3. Two-year survival
4. Five-year survival
5. Relapse free survival (RFS). Duration of follow-up: 60 months from the date of surgery.

Overall trial start date


Overall trial end date


Reason abandoned (if study stopped)


Participant inclusion criteria

1. Patients who have undergone complete macroscopic resection for ductal adenocarcinoma of the pancreas (R0 or R1 resection)
2. Completion of all pre-operative investigations
3. Histological confirmation of the primary diagnosis
4. Histological examination of all resection margins
5. No evidence of malignant ascites, liver metastasis, spread to other distant abdominal organs, peritoneal metastasis, spread to extra-abdominal organs - CT scan within 3 months prior to randomisation
6. A World Health Organization performance status less than 2
7. Fully recovered from the operation and fit to take part in the trial
8. Able to attend for administration of the adjuvant therapy
9. Able to attend for long-term follow-up
10. Life expectancy greater than 3 months
11. No previous or concurrent malignancy diagnoses (except curatively-treated basal cell carcinoma of skin, carcinoma in situ of cervix)
12. No serious medical or psychological condition precluding adjuvant treatment
13. Fully informed written consent given

Participant type


Age group




Target number of participants


Participant exclusion criteria

1. Use of neo-adjuvant chemotherapy or other concomitant chemotherapy
2. Patients with pancreatic lymphoma
3. Macroscopically remaining tumour (R2 resection)
4. Patients with Tumor-Node-Metastasis (TNM) Stage IVb disease
5. Patients younger than 18 years
6. Pregnancy
7. New York Heart Association Classification Grade III or IV
8. Previous chemotherapy
9. All men or women of reproductive potential, unless using at least two contraceptive precautions, one of which must be a condom
10. Patients with known malabsorption

Recruitment start date


Recruitment end date



Countries of recruitment

France, Germany, Sweden, United Kingdom

Trial participating centre

106 hospitals

Sponsor information


University of Liverpool and the Royal Liverpool and Broadgreen University Hospital NHS Trust (UK)

Sponsor details

c/o Mrs Lindsay Carter
Research and Business Services
The Foresight Centre
3 Brownlow Street
L69 3GL
United Kingdom

Sponsor type




Funder type


Funder name

Cancer Research UK (CRUK) (UK) - funding the central co-ordination of the trial (the Liverpool Cancer Trials Unit) (grant ref: C245/A8968)

Alternative name(s)

Funding Body Type

Funding Body Subtype


Funder name

National Cancer Research Network (NCRN) nurse support at UK sites. Non-UK sites will be required to secure their own funding for participating in the trial.

Alternative name(s)

Funding Body Type

Funding Body Subtype


Results and Publications

Publication and dissemination plan

PDAC cohort: 2-year analysis expected late 2016/early 2017; 5-year analysis late 2019/early 2020
Periampullary cohort: 4-year analysis but unsure of the date – we have requested an extension to the recruitment period.

Intention to publish date


Participant level data

Available on request

Basic results (scientific)

Publication list

2017 results in:

Publication citations

Additional files

Editorial Notes

30/01/2017: Publication reference added. 26/05/2016: The target number of participants has been updated from 1080 to 722. 11/09/2015: The overall trial end date was changed from 01/11/2014 to 31/10/2017.