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 |
| EudraCT/CTIS number | 2007-004299-38 |
| ClinicalTrials.gov number | NCT00058201 |
| Secondary identifying numbers | ESPAC-4 |
- 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
Contact information
Prof John Neoptolemos
Scientific
Scientific
University of Liverpool
Division of Surgery and Oncology
The Duncan Building
Daulby Street
Liverpool
L69 3GA
United Kingdom
Dr Karl Harvey
Public
Public
University of Liverpool
Division of Surgery and Oncology
The Duncan Building
Daulby Street
Liverpool
L69 3GA
United Kingdom
Study information
| Study design | Phase III international randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient 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 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(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 |
| Condition | 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | 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 study start date | 13/10/2008 |
| Overall study end date | 31/10/2017 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 722 |
| Total final enrolment | 730 |
| 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 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 | 13/10/2008 |
| Recruitment end date | 31/10/2017 |
Locations
Countries of recruitment
- France
- Germany
- Sweden
- United Kingdom
Study participating centre
106 hospitals
-
United Kingdom
United Kingdom
Sponsor information
University of Liverpool and the Royal Liverpool and Broadgreen University Hospital NHS Trust (UK)
University/education
University/education
c/o Mrs Lindsay Carter
Research and Business Services
The Foresight Centre
3 Brownlow Street
Liverpool
L69 3GL
England
United Kingdom
| Website | http://www.liv.ac.uk |
|---|---|
"ROR" |
https://ror.org/009sa0g06 |
Funders
Funder type
Charity
Cancer Research UK (CRUK) (UK) - funding the central co-ordination of the trial (the Liverpool Cancer Trials Unit) (grant ref: C245/A8968)
No information available
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.
No information available
Results and Publications
| Intention to publish date | 30/06/2017 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| 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. |
| 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 | |
| Plain English results | 26/10/2022 | No | Yes | ||
| Results article | 05/12/2024 | 31/03/2025 | Yes | No |
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.
