A trial comparing gemcitabine alone with gemcitabine and capecitabine together after surgery to remove cancer of the pancreas

ISRCTN	ISRCTN96397434
DOI	https://doi.org/10.1186/ISRCTN96397434
ClinicalTrials.gov (NCT)	NCT00058201
Clinical Trials Information System (CTIS)	2007-004299-38
Protocol serial number	ESPAC-4
Sponsor	University of Liverpool and the Royal Liverpool and Broadgreen University Hospital NHS Trust (UK)
Funders	Cancer Research UK (CRUK) (UK) - funding the central co-ordination of the trial (the Liverpool Cancer Trials Unit) (grant ref: C245/A8968), 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.

Submission date: 07/08/2007
Registration date: 08/02/2008
Last edited: 31/03/2025

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

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-at-chemotherapy-after-surgery-to-remove-cancer-of-the-pancreas-espac-4

Contact information

Prof John Neoptolemos
Scientific

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

Dr Karl Harvey
Public

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

Study information

Primary study design	Interventional
Study design	Phase III international randomised controlled trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	European Study Group for Pancreatic Cancer (ESPAC) - Trial 4: combination versus single agent adjuvant chemotherapy in resectable pancreatic cancer
Study acronym	ESPAC-4
Study objectives	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(s)	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
Health condition(s) or problem(s) studied	Resectable pancreatic cancer
Intervention	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	Drug
Phase	Phase III
Drug / device / biological / vaccine name(s)	Gemcitabine, capecitabine
Primary outcome measure(s)	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.
Key secondary outcome measure(s)	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.
Completion date	31/10/2017

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	All
Target sample size at registration	722
Total final enrolment	730
Key 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
Key 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
Date of first enrolment	13/10/2008
Date of final enrolment	31/10/2017

Locations

Countries of recruitment

United Kingdom
France
Germany
Sweden

Study participating centre

106 hospitals

-
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
IPD sharing plan	The datasets generated during and/or analysed during the current study are/will be available upon request

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	11/03/2017		Yes	No
Results article		05/12/2024	31/03/2025	Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Plain English results			26/10/2022	No	Yes

Editorial Notes

31/03/2025: Publication reference added.
25/10/2022: Cancer Research UK plain English results link added.
05/09/2019: The following changes have been made:
1. Publication reference added.
2. The final enrolment number has been added from the reference.
3. The NCT code has been added.
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.