Condition category
Cancer
Date applied
07/08/2007
Date assigned
08/02/2008
Last edited
26/05/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Contact information

Type

Scientific

Primary contact

Prof John Neoptolemos

ORCID ID

Contact details

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

Type

Public

Additional contact

Dr Karl Harvey

ORCID ID

Contact details

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

Additional identifiers

EudraCT number

2007-004299-38

ClinicalTrials.gov number

Protocol/serial number

ESPAC-4

Study information

Scientific title

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

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.

On 11/09/2015 the overall trial end date was changed from 01/11/2014 to 31/10/2017.

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

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

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

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

Phase

Phase III

Drug names

Gemcitabine, capecitabine

Primary outcome measures

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

13/10/2008

Overall trial end date

31/10/2017

Reason abandoned

Eligibility

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

Patient

Age group

Adult

Gender

Both

Target number of participants

722

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

Trial participating centre

106 hospitals
-

Sponsor information

Organisation

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
Liverpool
L69 3GL
United Kingdom

Sponsor type

University/education

Website

http://www.liv.ac.uk

Funders

Funder type

Charity

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

Location

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

Location

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

30/06/2017

Participant level data

Available on request

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

26/05/2016: The target number of participants has been updated from 1080 to 722.