Liverpool

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Overview

Our Centre

The primary strategic areas of the Liverpool ECMC are pancreatic cancer and haemato-oncology, with expertise in cancer biology and pharmacology to develop novel biomarkers of efficacy, resistance and drug safety. Other areas of focus supported by local expertise are breast cancer with brain metastases, hepatobiliary cancers, head & neck cancers and uveal melanoma.

Liverpool ECMC has internationally renowned expertise in pancreas cancer. In the translational setting work is ongoing in the development of stratified approaches to treatment. We are utilising our extensive biobanks and Good Clinical Practice Laboratory Facility to discovery and validate potential biomarkers for use in clinical trials (specifically using immunohistochemistry and protein/RNA in situ). We have ongoing pre-clinical commercial collaborations in this setting.

In the phase I setting, we have a portfolio encompassing a wide range of tumour types encompassing all our strategic areas. Our expertise particularly lies in primary hepatocellular carcinoma phase I trials.

Our patient population

For 2019 there were 9494 new patients with 846 enrolled on clinical trials.

Organisations affiliated with the Liverpool ECMC:

Our location

The Liverpool ECMC is situated North West England. By air, Liverpool ECMC can be reached via Liverpool John Lennon Airport (30 minutes by road). Manchester Airport is also less than 1 hour away via road. Liverpool also has good rail links (via Liverpool Lime Street Station) and road links (from the M6 the M62, M57 and M56 can be taken to the city centre).

Contact the Centre Manager:

Charlotte Rawcliffe

Sara.Harrison@liverpool.ac.uk

liverpool-ecmc@liverpool.ac.uk

Address

ADULT:

Liverpool Experimental Cancer Medicine Centre

Liverpool Clinical Trials Centre

University of Liverpool

1^st Floor Block C, Waterhouse Building

3 Brownlow Street

Liverpool

L69 3GL

PAEDIATRICS:

Alder Hey Children's Hospital
Eaton Road
West Derby
Liverpool, L12 2AP

Team Members

Professor Dan Palmer

Adult Centre Lead

Expertise:

Adult

palmerd@liverpool.ac.uk

Professor Daniel Palmer took his current position of North West Cancer Research Chair in Medical Oncology at the University of Liverpool in 2011. His research interests relate to HPB cancers (liver, pancreas and biliary tract) and incorporate basic laboratory science, translational research and clinical trials. He has established a portfolio of early phase clinical trials and translational studies in this field as well as making significant contributions to multi-centre phase III trials. His laboratory research is currently investigating novel therapeutic approaches to the treatment of HPB cancer through stimulation of anti-tumour immune responses and targeting tumour micro-environment, and developing and validating biomarkers for a stratified approach to the treatment of pancreatic cancers. He is a member of the UK NCRN Upper GI cancers clinical studies group, and the hepatobiliary and pancreatic sub-groups. He is Director of the Cancer Research UK/NIHR Liverpool Experimental Cancer Medicine Centre.

Prof Bill Greenhalf

Scientific Lead and Deputy Director for Good Clinical Practice Laboratories

Expertise:

Adult

greenhaf@liverpool.ac.uk

Bill Greenhalf is a Professor in Medical Oncology in the University of Liverpool and is the Director of the Liverpool Good Clinical Practice Laboratory Facility. He came to Liverpool in 1997 from Novartis in Basel, having previously worked at the State University of São Paulo in Brazil. He was awarded a doctorate from the University of Manchester in 1990. He is the lead scientist of the European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer (EUROPAC) and is the chair of the ECMC Quality Assurance and Translational Science (QATS) group.

Charlotte Rawcliffe

Operational Director

Expertise:

Adult

c.rawcliffe@liverpool.ac.uk

+44 (0)151 794 8167

Charlotte is the Operational Lead for Cancer within the Liverpool Clinical Trials Centre and is responsible for the set-up and management of the cancer trials portfolio in accordance with the UK Clinical Trials Regulation. Charlotte did her undergraduate degree in Microbiology at the University of Sheffield before completing a MSc in genetic Epidemiology. She moved into Clinical Trials over 15 years and has worked in academia and industry, delivering a broad range of Phase I–IV clinical trials across a range of tumour types and therapeutic areas.

Ruth Stafferton

Cancer Research UK Senior Research Nurse and PPIE (Patient and Public Involvement and Engagement) Lead

Ruth was awarded in 1995 Dip HE Health Care Studies and Nursing (Adult Branch) at Berkshire College of Nursing and Midwifery (University of Reading) She has worked in research at St Mark’s Hospital Polyposis Registry, The Royal Marsden Hospital, and Lancashire Teaching Hospitals NHS Trust. In 2012 Ruth was appointed Cancer Research UK Senior Research Nurse (Liverpool) and is based in Liverpool Clinical Trials Centre, University of Liverpool.

Scientific & Operational Team

Dr Lisa Howell

Lead

Expertise:

Paediatric

lisa.howell@alderhey.nhs.uk

Adult Expertise

Treatment Modalities

Gene therapy

Immunotherapy

Oncolytic viruses

Small Molecules

Surgery

Facilities/Translational Research

Dedicated 24 hour stay facilities (including weekends)
On-site pharmacy
Biobanking facilities
Dedicated research staff
Snap freezing facilities
On-site central lab

1. Liverpool Good Clinical Practice Laboratory Facility

The Liverpool GCP Laboratory Facility has expertise in translational sample collection and logistics and extensive experience of acquiring, storing and analysing high quality human biological samples linked to anonymised trials.

The Facility can provide assay support in clinical trials across the ECMC Network and has expertise in the following:

Immunohistochemistry and in-situ hybridisation (RNAScope).
Proliferation assays (T-cell response to immune therapy and vaccines).
Cytokine quantification using Luminex (various panels but principally 27plex from BioRad).
Minimal Residual Disease (MRD) by FACS analysis.
TP53 codon 31 SNP analysis (in CLL) by FACS analysis.
Real Time PCR analysis.
Limiting dilution NGS analysis of Tp53 (for CTC detection and analysis).

The Facility can undertake bespoke assay validation on request.

Current validated assays include: CK18, M30/M65, NEFA, Cytokine Panel (27), Creatinine, KIM-1, T cell proliferation, hENT-1 and MRD.

2. QATS Assay Validation Project

Prof Bill Greenhalf, Liverpool ECMC Scientific Lead, is leading a project on sharing assay validations across the network, as part of his remit at the QATS group lead.

If you would like to take part in this project please contact Prof Greenhalf on greenhaf@liverpool.ac.uk

Cancer Types

We have expertise in both solid tumours and haematological malignancies.

The research areas of interest of the Liverpool ECMC include:

Pancreatic Cancer
Haemato-oncology
Hepatobiliary Cancers
Breast Cancers with Brain Metastases
Head and Neck Cancers
Uveal Melanoma

Drugs/Treatment Modalities

Radiotherapy/immuno-oncology combinations
Combination therapies

Radiotherapy

We have regular access to both photon and proton radiotherapy. We have research expertise in the following:

Volumetric Modulated Arc Therapy (VMAT)
Intensity Modulated Radiotherapy (IMRT)
Image Guided Radiotherapy (IGRT)
4-Dimensional Radiotherapy (4D-RT)
Stereotactic Radiotherapy (SBRT/SABR)
Radiosurgery

Molecular Diagnostic Testing

We have the following available on a routine basis to our patients:

Disease specific NGS panel testing (next generation sequencing)
Large NGS panel testing

This is available for tumours and for ctDNA (circulating tumour DNA)

Paediatric Expertise

Liverpool is an ITCC accredited centre, is part of the Adult and Paediatric Networks and has established close working links with other UK ITCC centres (particularly Leeds and Manchester). It is well located for geographically distributed studies for the North of England, Wales and Ireland.

There are close links with the Paediatric Cancer Biology Group of Liverpool University and the Liverpool CRCTU, with work focusing on neuroblastoma and medulloblastoma and relationships are being established with the adult ECMC. There is an established and reliable functional imaging department which includes the use of an intraoperative 3T MR scanner.

Finally, the hospital is able to provide accommodation for families of patients in the form of The Ronald McDonald Home away from Home provision which will make it easier for families needing to travel to Alder Hey for early phase clinical trials.

Case Study

Case Studies

1. ARACHNID Trial Development and Radiotherapy/Immune-oncology Combination Expertise and Capability

The Liverpool ECMC is leading and co-ordinating the ARACHNID phase II, multi-arm, adaptive trial of durvalumab and tremelimumab in combination with different radiotherapy modalities for advanced hepatocellular carcinoma (Chief Investigator: Prof Daniel Palmer, Liverpool ECMC Lead).

This trial, which is only the second academic proton study, has been developed in collaboration with colleagues from across the ECMC Network: Prof Maria Hawkins (Co-CI & Radiotherapy Lead - Oxford), Prof Tim Meyer (Co-Investigator – UCL) and Dr Ganesh Radhakrishna (Proton Lead – Manchester).

This trial provides a unique opportunity to assess the combination of checkpoint inhibitors with stereotactic body radiation therapy (SBRT) and also β-particle brachytherapy & protons to determine how different radiotherapy modalities may influence immune responses.

ECMC support has been crucial in development of this trial. In Liverpool, ECMC funded staff have designed the trial and developed the clinical and translational protocol and will continue to support the set-up and delivery of this trial.

This trial adds to the increasing portfolio of radiotherapy/immune-oncology combination trials led by Liverpool (NICO, RADIANT-BC) and is underpinned by local translational and pre-clinical research in the radiotherapy and radiobiology fields.

Bio-samples collected as part of this portfolio will be available to the ECMC Network.

2. Development of hENT1 as an IHC Biomarker

A key aspect of our translational research programme is identifying therapeutic biomarkers for use in the clinical management of cancer. There are currently no predictive biomarkers available to guide treatment of pancreatic ductal adenocarcinoma (PDAC), a disease with a notoriously poor prognosis.

We have previously shown that tumour equilibrative nucleoside transporter 1 (hENT1) levels predict response to adjuvant gemcitabine in PDAC, using samples from a large phase 3 randomised clinical trial, ESPAC-3. Work is currently underway examining if the predicted poor response to gemcitabine conferred by low levels of intratumoural hENT1 can be overcome by combination with capecitabine, utilising samples from the ESPAC-4 study.

To test if hENT1 may have utility in the advanced setting, analysis is also currently ongoing of hENT1 levels in core biopsies from locally advanced primary tumour and distant metastases, as part of the ACELERATE randomised clinical trial.

By examining hENT1 alongside other potential biomarkers associated with chemotherapy uptake and metabolism, we aim to generate a panel of candidates for guiding therapy based on tumour molecular profiles.

Publications

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Scientific & Operational Team