Selective Chemoradiation in Advanced LOcalised Pancreatic cancer

ISRCTN	ISRCTN96169987
DOI	https://doi.org/10.1186/ISRCTN96169987
ClinicalTrials.gov (NCT)	NCT01032057
Clinical Trials Information System (CTIS)	2008-001394-15
Protocol serial number	Protocol no: WCTU012; Sponsorship no: SPON 415-07; EudraCT: 2008-001394-15
Sponsor	Cardiff University (UK)
Funders	Cancer Research UK (CRUK) (UK) (ref: C28958/A9355) - funded by a grant from the Feasibility Study Committee (FSC), The Wales Cancer Trials Unit (WCTU) is core funded by CRUK and WCTU core resources will be used to support this trial.

Submission date: 08/04/2008
Registration date: 29/05/2008
Last edited: 14/02/2020

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.cancerhelp.org.uk/trials/a-trial-of-chemotherapy-followed-by-chemoradiotherapy-for-locally-advanced-pancreatic-cancer

Contact information

Dr Somnath Mukherjee
Scientific

Velindre NHS Trust
Velindre Road
Whitchurch
Cardiff
CF14 2TL
United Kingdom

Phone	+44 (0)2920 196184
Email	Somnath.mukherjee@velindre-tr.nhs.wales.uk

Study information

Primary study design	Interventional
Study design	Multi-centre phase II randomised trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	A multi-centre randomised phase II study of induction chemotherapy followed by gemcitabine or capecitabine based chemoradiotherapy (CRT) for locally advanced non-metastatic pancreatic cancer
Study acronym	SCALOP
Study objectives	Pancreatic cancer is the tenth most common cancer in the UK with nearly 7,000 patients being diagnosed in UK each year and mortality parallels its incidence indicating that an effective treatment is required. Localised inoperable cancer accounts for 30 - 40% of advanced disease and its optimal management is unclear. Chemotherapy alone is the predominant modality in the UK whilst CRT is the treatment of choice in the USA. It has been reported that patients receiving either modality have a median survival of around 10 months. Gemcitabine is the established monotherapy for pancreatic cancer; its combination with erlotinib and capecitabine have produced small improvements in median survival of 0.5 and 1.4 months respectively. The rationale for additional loco-regional therapy includes prolongation of local control and downstaging of inoperable disease, both of which may improve survival. Advancement in radiation technique has minimised radiation toxicity and combined with improved patient care makes CRT a feasible option. A national survey through the pancreatic sub-group of ACORRN (Academic Clinical Oncology, Radiotherapy and Radiobiology Network) has shown that the use of CRT is fragmented across the UK with no consensus guidelines. The SCALP phase II study is a feasibility study which attempts to evaluate the activity, safety and feasibility of two chemoradiation treatment in the management of locally advanced non-metastatic pancreatic cancer (LANPC). If either is found to be active, safe and feasible to use it may be considered as experimental arm(s) of a future phase III trial. Also it will attempt to define an acceptable CRT strategy in UK and to demonstrate that high quality Radiotherapy (RT) with central Quality Assurance (QA) can be delivered. We hope to conclude as to whether or not there is sufficient evidence to warrant further investigation of one or both of the CRT regimes in a future phase III trial.
Ethics approval(s)	Protocol approval is being sought from a Multi-Centre Research Ethics Committee (MREC). Each participating centre will be approved through a Regional Ethics Committee (REC) prior to patient recruitment.
Health condition(s) or problem(s) studied	Localised advanced non-metastatic pancreatic cancer (LANPC)
Intervention	Patients will be recruited over a period of approximately 24 months. Patients satisfying inclusion and exclusion criteria will receive three cycles (12 weeks) of GEMCAP chemotherapy (each four-week cycle consists of gemcitabine 1000 mg/m^2 weekly for three weeks out of four and capecitabine 830 mg/m^2 twice daily [bd] daily for 21 days). If restaging computed tomography (CT) scan at 12 weeks confirms stable or responding disease encompassable in a radiation field, patients will be randomised to receive a CRT regimen consisting of a fourth cycle of GEMCAP (for three weeks) as above and either: 1. 50.4 Gy in 28 fractions over 5.5 weeks (1.8 Gy per fraction, Monday to Friday) and gemcitabine 300 mg/m^2 intraveous (IV) weekly for the duration of radiotherapy (RT), or 2. 50.4 Gy in 28 fractions over 5.5 weeks (1.8 Gy per fraction, Monday to Friday) and capecitabine 830 mg/m^2 bd (Monday to Friday) for the duration of RT Radiotherapy will be planned conformally using single phase, three to four coplanar beams, using 6 - 10 MV photons, treating all fields daily Monday to Friday. Those who fail on chemotherapy at 12 weeks will be treated and followed up according to clinician's choice, but they will be followed up and data on treatment and death will be collected. Total treatment duration is 22 weeks from screening until follow up; patients will be followed up until week 52.
Intervention type	Drug
Phase	Phase II
Drug / device / biological / vaccine name(s)	Gemcitabine, capecitabine
Primary outcome measure(s)	In each arm of the trial: nine-month (from registration) progression-free survival, defined according to the RECIST (Response Evaluation Criteria in Solid Tumours) criteria
Key secondary outcome measure(s)	In each arm of the trial: 1. Toxicity, during and after treatment using National Cancer Institute Common Terminology Criteria for Adverse Events version three (NCI CTCAE v 3.0). Toxicity will be measured at baseline, weeks 5, 9, 13 (i.e. at the end of each GEMCAP cycle - prior to CRT), 17, 18, 19, 20, 21, 22 (during CRT), 23, 26, 39 and 52 (follow-up). Also, serious adverse events (SAEs) will be collected in real time. 2. Quality of life, measured at baseline, week 17, 23, 26, 39 and 52 3. Overall 12-month survival and time from registration to death by any cause. Those still alive will be censored at date last seen. 4. Objective disease response (based on RECIST criteria) 5. Progression-free survival (time to event). Time from registration to any progression (based on RECIST criteria) and/or death. Those progression-free and alive will be censored at date last seen. 6. Radiotherapy quality assurance (RT QA); planning will be between weeks 13 - 16, planned assessment will be during week 17 7. Tumour marker CA19-9, measured at baseline, weeks 17, 39 and 52
Completion date	31/05/2010

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	100
Key inclusion criteria	1. Informed consent 2. Aged greater than or equal to 18 years, either sex 3. Histologically or cytologically confirmed inoperable (or medically unfit for surgery) adenocarcinoma of the pancreas 4. Chosen for non-surgical therapy by a specialised Multi-Disciplinary Team 5. World Health Organization (WHO) performance status 0 - 2 6. Neutrophils greater than or equal to 1.5 x 10^9/L, platelets greater than or equal to 100 x 10^9/L and haemoglobin greater than or equal to 10 g/dL 7. Adequate liver function tests: 7.1. Serum bilirubin less than 35 μmol/l. In patients who have had a recent biliary drain and whose bilirubin is descending, a value of less than or equal to 50 µmol/L is acceptable. 7.2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 2.5 x upper limit of normal (ULN) 7.3. Alkaline phosphatase less than or equal to 5 x ULN 8. Adequate renal function (glomerular filtration rate [GFR] greater than 50 ml/min Cockcroft and Gault) 9. Women and men of child-bearing potential should agree to use an adequate contraception method, which must be continued for three months after completion of chemotherapy
Key exclusion criteria	1. Women who are pregnant or breast feeding 2. Any evidence of severe uncontrolled systemic diseases including uncontrolled coronary artery disease 3. Any patient with myocardial infarction or stroke within the last six months 4. No previous malignancies in the preceding five years except for in situ cancer of the uterine cervix and adequately treated basal cell skin carcinoma and early stage malignancy 5. Renal abnormalities such as polycystic kidneys or hydronephrosis or ipsilateral single kidney 6. Previous radiotherapy to upper abdomen 7. Recurrent cancer following definitive pancreatic surgery
Date of first enrolment	01/06/2008
Date of final enrolment	31/05/2010

Locations

Countries of recruitment

United Kingdom
Wales

Study participating centre

Velindre NHS Trust

Cardiff
CF14 2TL
United Kingdom

Results and Publications

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

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/04/2013		Yes	No
Results article	results	15/11/2015		Yes	No
Results article	results	01/08/2016	14/02/2020	Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Plain English results				No	Yes

Editorial Notes

14/02/2020: ClinicalTrials.gov number and publication reference added.
18/10/2018: Cancer Research UK lay results summary link added to Results (plain English).
09/02/2016: Publication reference added.
08/02/2011: The overall trial end date was changed from 31/05/2010 to 21/07/2011 and the target number of participants has changed from 76 to 100.
29/07/2008: The acronym for this trial was changed from 'SCALP' to 'SCALOP' following a suggestion from the ethics committee.