ESPAC-5: European Study group for Pancreatic Cancer - Trial 5

ISRCTN	ISRCTN89500674
DOI	https://doi.org/10.1186/ISRCTN89500674
Clinical Trials Information System (CTIS)	2013-003932-56
Protocol serial number	16201
Sponsor	University of Liverpool (UK)
Funder	Cancer Research UK (UK)

Submission date: 03/04/2014
Registration date: 03/04/2014
Last edited: 16/12/2022

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

http://www.cancerresearchuk.org/cancer-help/trials/a-study-looking-at-chemotherapy-or-chemoradiotherapy-before-surgery-for-pancreatic-cancer-espac-5f

Contact information

Mrs Karen Scott
Scientific

Cancer Research UK Liverpool Cancer Trials Unit
University of Liverpool , 1st floor Block C
Waterhouse Building 3 Brownlow Street
Liverpool
L69 3GL
United Kingdom

Email	K.Billington@liv.ac.uk

Study information

Primary study design	Interventional
Study design	Randomised; Interventional; Design type: Process of Care, Screening, Treatment
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	ESPAC - 5: European Study Group for Pancreatic Cancer - Trial 5: four arm, prospective, multicentre, randomised feasibility trial of immediate surgery compared with neoadjuvant chemotherapies and neoadjuvant chemoradiotherapy
Study acronym	ESPAC-5
Study objectives	ESPAC-5: a multi-centre, prospective, randomised, feasibility Phase II trial comparing neoadjuvant therapy to immediate surgical exploration in patients with borderline resectable pancreatic cancer. The aim of this study will be to compare neoadjuvant chemotherapy (GemCap or FOLFIRINOX) or chemoradiotherapy with immediate surgery. All patients who undergo resection will also receive adjuvant chemotherapy as standard.
Ethics approval(s)	NRES Committee North West - Haydock, 18/03/2014, ref: 14/NW/0036
Health condition(s) or problem(s) studied	Topic: Cancer; Subtopic: Upper Gastro-Intestinal Cancer; Disease: Pancreas
Intervention	If eligible for the study patients will be randomised onto one of the following arms. Arm A (control): Surgery. Eligible patients will undergo surgical exploration for resection within two weeks of randomisation. Following recovery from successful resection (up to 12 weeks) patients will undergo standard adjuvant chemotherapy either gemcitabine or 5-fluorouracil for six cycles ie. 24 weeks. If patients do not undergo successful resection then following recovery from surgery, further therapy will be as physicians choice. Patients will be followed up for 12 months after randomisation. Arm B: GEMCAP. Within two weeks of randomisation, eligible patients will commence neoadjuvant Gemcitabine, 1000mg/m2 iv infusion over 30 mins, once a week for 3 of 4 weeks and capecitabine 830mg/m2 BD PO for 21 /28d, (one cycle) for 2 cycles i.e. 8 weeks . Four to six weeks after completion chemotherapy patients will undergo staging CT scan. If there has been no progression patients will then undergo surgical exploration within two weeks as for Arm A. Arm C: FOLFIRINOX - Within two weeks of randomisation, eligible patients will commence neoadjuvant Oxaliplatin 85mg/m2, Irinotecan 180mg/m2, Folinic acid 400mg/m2, 5-FU 2400mg/m2 46 hour infusion, repeated every 2 weeks for 4 cycles. Growth factor support may be administered at the investigators discretion. Four to six weeks after completion chemotherapy patients will undergo staging CT scan. If there has been no progression patients will then undergo surgical exploration within two weeks as for Arm A. Arm D: CRT. Within two weeks of randomisation, eligible patients will commence neoadjuvant CRT delivering a total dose of 50.4Gy in 28 daily fractions over 5 1/2 weeks (1.8Gy/#fraction Mon to Fri) with Capecitabine 830mg/m2 BD PO (Mon to Fri) throughout radiotherapy. Centres would be required to choose to use IMRT (preferred) or 3D conformal RT for all their patients. Four to six weeks after completion CRT patients will undergo staging CT scan. If there has been no progression patients will then undergo surgical exploration within two weeks as for Arm A. Patients will be followed up for 12 months after randomisation.
Intervention type	Mixed
Primary outcome measure(s)	1. Recruitment rate Recruitment rate will be measured by the proportion of centres that successfully engage in the study and by the overall recruitment. Centres will be classified as successfully engaged if the study has opened in a timely fashion and if they are achieving over 50% of the recruitment and randomisation rate estimated for their centre. The overall recruitment rate will be deemed successful if at least 80% of the centres have fully engaged in the study and the target rate has been achieved (100 patients in 24 months). 2. Resection rate An overall resection rate will be measured using the total number of patients at baseline. A second resection rate will also be measured using only the patients who undergo explorative surgery. R1 and R0 resection margins will be used when measuring the resection rate R2 resection margins will be excluded.
Key secondary outcome measure(s)	Not provided at time of registration
Completion date	30/01/2021

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	100
Total final enrolment	90
Key inclusion criteria	1. Borderline resectable mass in the pancreatic head as defined by CT criteria 2. Histologically or cytologically proven pancreatic ductal adenocarcinoma (including variants) 3. Able to undergo biliary drainage using a fully covered self expanding metal stent 4. Age >= 18 years 5. WHO performance status 0, 1 6. Platelets >100 x 109/l; WBC > 3 x 109/l; neutrophils > 1.5 x 109/l 7. Serum bilirubin =1.5 ULN 8. Calculated creatinine clearance > 50ml/min 9. Able to comply with protocol requirements and deemed fit for surgical resection, chemotherapy and radiotherapy. 10. Written informed consent; Target Gender: Male & Female ; Lower Age Limit 18 years
Key exclusion criteria	1. Distant metastatic disease 2. History of previous or concurrent malignancy diagnoses (except curatively-treated basal cell carcinoma of skin, carcinoma in situ of cervix) 3. Serious medical or psychological condition precluding neoadjuvant treatment and surgical resection 4. Previous chemotherapy or chemoradiotherapy 5. Pregnancy 6. WHO performance status 24 7. New York Heart Association Classification Grade III or IV 8. Patients with known malabsorption
Date of first enrolment	26/08/2014
Date of final enrolment	31/12/2018

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

Cancer Research UK Liverpool Cancer Trials Unit

Liverpool
L69 3GL
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary
IPD sharing plan	Not provided at time of registration

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article		12/12/2022	16/12/2022	Yes	No
Basic results		12/02/2022	20/05/2022	No	No
HRA research summary			28/06/2023	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

16/12/2022: The following changes were made to the trial record:
1. Publication reference added.
2. The total final enrolment was added.
02/09/2022: Internal review.
20/05/2022: EU Clinical Trials Register results added.
20/01/2021: The following changes have been made:
1. The overall trial end date has been changed from 31/12/2019 to 30/01/2021.
2. The intention to publish date has been changed from 31/12/2020 to 01/04/2021.
15/01/2019: The intention to publish date, 31/12/2020, was added.
27/09/2018: The following changes were made to the trial record:
1. The recruitment end date was changed from 26/08/2016 to 31/12/2018.
2. The overall trial end date was changed from 01/08/2017 to 31/12/2019.
22/07/2015: The overall trial end date was changed from 01/04/2015 to 01/08/2017.