Plain English Summary
Trial website
Contact information
Type
Scientific
Primary contact
Dr Somnath Mukherjee
ORCID ID
Contact details
Velindre NHS Trust
Velindre Road
Whitchurch
Cardiff
CF14 2TL
United Kingdom
+44 (0)2920 196184
Somnath.mukherjee@velindre-tr.nhs.wales.uk
Additional identifiers
EudraCT number
2008-001394-15
ClinicalTrials.gov number
NCT01032057
Protocol/serial number
Protocol no: WCTU012; Sponsorship no: SPON 415-07; EudraCT: 2008-001394-15
Study information
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
Acronym
SCALOP
Study hypothesis
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
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.
Study design
Multi-centre phase II randomised 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
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 names
Gemcitabine, capecitabine
Primary outcome measure
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
Secondary outcome measures
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
Overall trial start date
01/06/2008
Overall trial end date
31/05/2010
Reason abandoned (if study stopped)
Eligibility
Participant 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
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
100
Participant 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
Recruitment start date
01/06/2008
Recruitment end date
31/05/2010
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Velindre NHS Trust
Cardiff
CF14 2TL
United Kingdom
Sponsor information
Organisation
Cardiff University (UK)
Sponsor details
FOA: Chris Shaw
Research Governance Coordinator
Research and Development
McKenzie House
30 - 36 Newport Road
Cardiff
CF24 0DE
United Kingdom
-
shawc3@cardiff.ac.uk
Sponsor type
University/education
Website
Funders
Funder type
Charity
Funder name
Cancer Research UK (CRUK) (UK) (ref: C28958/A9355) - funded by a grant from the Feasibility Study Committee (FSC)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
The Wales Cancer Trials Unit (WCTU) is core funded by CRUK and WCTU core resources will be used to support this trial.
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2013 results in: https://www.ncbi.nlm.nih.gov/pubmed/23474363
2015 results in: https://www.ncbi.nlm.nih.gov/pubmed/26530749
2016 results in: https://www.ncbi.nlm.nih.gov/pubmed/27497804 (added 14/02/2020)
Publication citations
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Results
Mukherjee S, Hurt CN, Bridgewater J, Falk S, Cummins S, Wasan H, Crosby T, Jephcott C, Roy R, Radhakrishna G, McDonald A, Ray R, Joseph G, Staffurth J, Abrams RA, Griffiths G, Maughan T, Gemcitabine-based or capecitabine-based chemoradiotherapy for locally advanced pancreatic cancer (SCALOP): a multicentre, randomised, phase 2 trial., Lancet Oncol., 2013, 14, 4, 317-326, doi: 10.1016/S1470-2045(13)70021-4.
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Results
Hurt CN, Mukherjee S, Bridgewater J, Falk S, Crosby T, McDonald A, Joseph G, Staffurth J, Abrams RA, Blazeby JM, Bridges S, Dutton P, Griffiths G, Maughan T, Johnson C, Health-Related Quality of Life in SCALOP, a Randomized Phase 2 Trial Comparing Chemoradiation Therapy Regimens in Locally Advanced Pancreatic Cancer, Int J Radiat Oncol Biol Phys, 2015, 93, 4, 810-818, doi: 10.1016/j.ijrobp.2015.08.026.