Glasgow

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Overview

Our Centre

The Glasgow ECMC develops and delivers early phase clinical trials and later phase clinical trials with translational endpoints.

These include leading and participating in commercial studies building on our existing relationships with many pharma and biotech companies and also in non – commercial studies including those developed through industry collaborations, through the CR-UK Centre for Drug Development, through Blood Cancer UK’s Trial Acceleration Programme, and through participation in non-commercial multi-arm stratified studies.

Key priorities for the Glasgow ECMC include, but are not limited to, drug development including Phase I trials, tumour agnostic, and pan-tumour basket clinical trials; tumour-specific early phase clinical trials with a focus on hepato-biliary–pancreatic cancers, GI cancers (colorectal and gastro-oesophageal), ovarian, breast, urological cancers, gliomas, melanoma and CML; drug-radiotherapy combinations, DNA damage response, novel immunotherapeutics, targeting the tumour microenvironment & stroma, inhibitors of signalling pathways and advanced cellular therapies.

For all of these clinical trials we maximise the biological and clinical data with pharmcodynamic biomarker studies in tumour and blood, and underpinned by precision medicine, exploiting tumour vulnerabilities for maximum patient benefit.

Tumour tissues collected as part of clinical studies are a valuable resource for exploratory biomarker studies across the UK cancer research network and via international consortia. This has catalysed collaboration with our basic science research programmes to enhance our research outputs and generate hypotheses to be tested in the clinical setting and utilising our strengths in pre-clinical cancer models.

ECMC resource also facilitates effective collaboration with other Centres within the ECMC network leading to the sharing of expertise and enhancing the training of our next generation of pre-clinical and clinical researchers in experimental medicine.

Our Patient Population

Approximately 11,000 NEW patients with adult solid tumours or haematological malignancies are referred to the Beatson West of Scotland Cancer Centre annually.

Approximately 800 patients were recruited into clinical trials in 2019, of which approximately 200 were recruited into ECMC studies with another approximately 100 patients recruited to provide tumour or blood samples (without a trial intervention) for biomarker or molecular profiling studies with external collaborators.

Organisations affliated with the Glasgow ECMC:

The University of Glasgow, including the CR-UK Beatson Institute, Glasgow
NHS Greater Glasgow & Clyde Health Board, which includes the Beatson West of Scotland Cancer Centre, Glasgow.
The Beatson West of Scotland Cancer Centre is also the regional Centre for non-surgical cancer treatment for the West of Scotland which also includes 3 other Health Boards (NHS Lanarkshire; NHS Ayrshire & Arran; NHS Forth Valley) representing a total population of approximately 2.5 million people.

Our location

The Glasgow Adult ECMC is based at the University of Glasgow (including the CR-UK Beatson Institute) and the Beatson West of Scotland Cancer Centre, Glasgow (and associated hospital sites within NHS Greater Glasgow & Clyde).

These campuses are located in the city of Glasgow, West of Scotland, less than 10 miles from Glasgow International Airport, which has regular scheduled flights to most UK regional airports and to several European and International destinations, and approximately 3 miles from the city’s mainline rail stations with excellent links to most other UK cities. Glasgow BioCity is a 20 acre biotech incubator campus located approximately 15 miles from the city.

The Beatson West of Scotland Cancer Centre is also the regional centre for non-surgical cancer treatment for the other Health Boards within the West of Scotland, with excellent road and rail links to the city of Glasgow.

Contact the Centre Manager:

Jeff Evans

j.evans@beatson.gla.ac.uk

Address

Cancer Research UK Beatson Laboratories
Switchback Road
Bearsden
Glasgow, G61 1BD

Royal Hospital for Sick Children
1345 Govan Road
Govan
Glasgow, G51 4TF

Beatson West of Scotland Cancer Centre
1053 Great Western Road
Glasgow

Paul O'Gorman Leukaemia Research Laboratories
1053 Great Wester Road
Glasgow

Wolfson-Wohl Cancer Research Centre
University of Glasgow

Team Members

Professor Jeff Evans

Centre Lead

Expertise:

Adult

j.evans@beatson.gla.ac.uk

+44 (0) 141 330 4171

He is Professor of Translational Cancer Research and the Clinical Lead, Institute of Cancer Sciences, University of Glasgow; Honorary Consultant in Medical Oncology, Beatson West of Scotland Cancer Centre, Glasgow; and Lead of the Glasgow ECMC.

His initial medical training was at St Bartholomew’s Hospital Medical School, University of London and he trained in Medical Oncology at Charing Cross Hospital Medical School and St George’s Hospital Medical School, London.

His research interests are in the pre-clinical and clinical development of novel anti-cancer agents and he leads the Phase I trials & drug development team in Glasgow. He is Chief Investigator of clinical trials in gastro-oesophageal and pancreatic cancers, and in HCC.

He is a member of the Gastro-Oesophageal Cancer sub-group and of the Pancreatic Cancer sub-group of the NCRI Upper GI Cancers study group, member of CR-UK’s Clinical Experts Review Panel, former member of CR-UK’s New Agents Committee and Feasibility Studies Committee, and he is co-editor of Clinical Subjects, British Journal of Cancer.

Dr Patricia Roxburgh

Senior Clinical Lecturer in Medical Oncology

Patricia.roxburgh@glasgow.ac.uk

Patricia Roxburgh is a Senior Clinical Lecturer in Medical Oncology specialising in early-phase clinical trials and management of ovarian cancer.

She was appointed as Senior Clinical Lecturer in Medical Oncology in April 2017 after completing medical oncology training in the West of Scotland. She obtained her PhD researching ‘Manipulation of the p53 pathway for cancer therapy’ at the CRUK Beatson Institute. On completion of training, she undertook a 12 month early clinical development fellowship at Roche in Manhattan, USA.

Patricia is Chief Investigator of the IMAGINE (Integrating Medically Actionable Genomics INto Early phase) trial which is designed to generate molecular profiles from contemporaneous tumour samples in a clinically useful timeframe.

Patricia has an ovarian cancer translational research group who work, in collaboration with Dr Seth Coffelt, to examine immunomodulation strategies in various models of ovarian cancer. She collaborates with ovarian cancer teams across Scotland on the Precision Medicine Scotland, high grade serous ovarian cancer whole-genome sequencing programme.

Professor Richard Wilson

Professor of Gastrointestinal Oncology

richard.h.wilson@glasgow.ac.uk

He graduated from Queen’s University Belfast in 1984 and then worked in Norhtern Ireland and Scotland as a junior doctor in surgery which included three years of colorectal cancer laboratory research at Queen's University, Belfast. He then retrained in clinical oncology before undertaking a post-CCT Fellowship in the National Cancer Institute in the USA in medical oncology and drug development.

He was appointed in 2001 as a Consultant and Senior Lecturer in Belfast City Hospital and Queen's University, Belfast. He set up the first early phase cancer clinical trials programme on the island of Ireland, and was the first Clinical Director of the Northern Ireland Cancer Trials Network.

His main interests are in gastrointestinal cancer (particularly colorectal cancer but also small bowel and anal cancer and peritoneal malignancies), in drug development, biomarkers, stratified medicine and early and late phase clinical trials.

His work includes cancer biology, translational and clinical research. After 17 years back in Belfast, he moved to the Institute of Cancer Sciences in the University of Glasgow and the Beatson West of Scotland Cancer Centre in early 2019 where he is Professor of Gastrointestinal Oncology and an Honorary Consultant in Medical Oncology.

Scientific & Operational Team

Professor Anthony Chalmers

Clinical Oncology

Anthony.Chalmers@glasgow.ac.uk

+44 (0) 141 330 6426

Professor Andrew Biankin

Regius Professor of Surgery

Andrew.Biankin@glasgow.ac.uk

+44 (0) 141 330 5670

Operational Team

Andrea Harkin

Glasgow CR-UK Clinical Trials Unit

Andrea.Harkin@glasgow.ac.uk

Ruth Orr

Senior clinical trial coordinator

Ruth.Orr@glasgow.ac.uk

Laura Rooney

CR-UK Lead Research & Information Nurse and PPIE (Patient and Public Involvement and Engagement Lead)

Laura.Rooney@glasgow.ac.uk

+44 (0) 141 301 7144

Adult Expertise

Treatment Modalities

Gene therapy

Immunotherapy

Small Molecules

Surgery

Facilities/Translational Research

CQC registered oncology trials unit
Dedicated 24 hour stay facilities (including weekends)
Radiopharmacy
On-site pharmacy
PK testing facilities
Biobanking facilities
Dedicated research staff
Snap freezing facilities
On-site central lab

Laboratory Collaborators

Translational Pharmacology Laboratory; Glasgow Precision Oncology Laboratory; Diagnostic & Molecular Pathology; CR-UK Beatson Institute & University of Glasgow; Leukaemia Research Labs

Clinical Facilities

Clinical Research Unit in the Beatson West of Scotland Cancer Centre which is a dedicated treatment unit for patients in early phase studies staffed by a team of 10 nurses, and with a fully equipped laboratory room. Beatson Clinical Research Facility consisting of 28 staff who support both early phase and late phase studies.

CRUK Glasgow Clinical Trials Unit that coordinates national and international studies with expertise in early phase academic studies and biomarker studies. Bone Marrow Transplant Unit including expertise in the delivery of Advanced Cellular Therapies (e.g. CAR-T, TILs) in both haematological malignancies and in solid tumours. Glasgow Molecular Pathology Node including the Glasgow Bio-Repository. RadNet which supports pre-clinical and clinical expertise in early phase evaluation of novel radiotherapy-drug combinations in glioblastoma, head & neck cancer, pancreatic, rectal and lung cancers, and mesothelioma

Laboatory & Translational Facilities

CR-UK Beatson Institute & the Institute of Cancer Sciences, University of Glasgow cancer vulnerabilities caused by energetic stress & aberrant metabolism; interplay between the tumour microenvironment, metastasis & recurrence; biology of early disease and ‘precision prevention’; haematopoietic stem cell biology; tumour immunology; DNA repair & radio-biology; Precision Oncology. Disease specific research is supported by a range of pre-clinical models and imaging resources.

Translational Pharmacology Laboratory with expertise in translational biomarker science and applied to transition preclinical programmes into early-phase clinical trials of novel cancer therapies. The TPL has developed a comprehensive and diverse inventory of GCLP assays for analysis of circulating, tissue and imaging biomarkers in cancer patients. By focusing on multiplex protein, nucleic acid and immune-biomarker ‘signatures’, the TPL aims to provide a deeper insight into the fundamental biological processes underlying drug-tumour interactions. These insights into the relationship between drug mechanism, disease biology and patient response aim to contribute to the development of strategies for individualising treatment, as well as shedding light on emerging disease mechanisms for future drug discovery. The TPL is a Cancer Research UK Biomarker ‘Hub’, working in collaboration with the Centre for Drug Development (CDD) to deliver biomarker studies for CDD’s clinical trial portfolio. Glasgow Precision Oncology Laboratory has a range of validated sequence-capture assays and workflows that are used to support clinical trials and trial-associated research.

Cancer Types

We have expertise in both solid tumours and haematological malignancies.

We have specific research expertise in the following:

Phase 1 Clinical Trials
Disease-specific Early Phase Trials in: Colorectal, HCC and Biliary Tract, Pancreatic, Gastro-Oesophageal, Urological, Ovarian, Lung, CNS tumours, Melanoma and Lymphoma
Drug-Radiotherapy Combinations: CNS, Head & Neck, Pancreas, Rectal
Advanced cellular therapies

Drug/Treatment Modalities

Advanced cellular therapies
Combination therapies
Oncolytic viral therapies
Drug-radiotherapy combinations

In addition to cytotoxic, antibody, immunotherapies, and small molecule targeted therapies, we have facilities for bone marrow transplantation and capabilities in advanced cellular therapies including CAR-T and TILs studies.

Radiotherapy

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

Intensity Modulated Radiotherapy (IMRT)
Image Guided Radiotherapy (IGRT)
4-Dimensional Radiotherapy (4D-RT)
Stereotactic Radiotherapy (SBRT/SABRT)
Radiosurgery
Internal Radiotherapy

Clinical expertise in early phase evaluation of novel radiotherapy-drug combinations.Site specific expertise in glioblastoma, head & neck cancer, pancreatic, rectal and lung cancers and mesothelioma. Preclinical expertise in evaluating novel radiotherapy based treatments in orthotopic models of cancer, with specific expertise in glioblastoma, pancreatic, rectal and lung cancers and mesothelioma. This work is supported by the CRUK RadNet Centre funding scheme.

Molecular Diagnostic Testing

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

Large NGS panel testing (next generation sequencing) via IMAGINE trial

This is available for tumour only.

Patients referred for an early phase clinical trial, who are fit for further systemic anticancer therapy can consent to the IMAGINE study. This involves contemporaneous tumour biopsy where feasible, when this is not feasible an archival tumour sample can be used. The tumour is then tested using the Glasgow Precision Oncology Lab sequence capture NGS assay (plus) which covers 356 genes.. The assay is currently research grade but validation is underway and it is expected to be validated for clinical use Q1 2021.

Paediatric Expertise

Glasgow ECMC Paediatric centre delivers phase I/II trials to children and young adults in Scotland and the North East of England.

The Haematology/Oncology Department of the Royal Hospital for Children in Glasgow is the largest UK CCLG centre in Scotland and sees approximately 90 new cases of cancer a year, of which two thirds are solid or brain tumours.

The clinical trials service is embedded within the Children and Young Adult Cancer Unit at The Royal Hospital for Children, Glasgow (opened June 2015).

In 2011 the Scottish Government established a Managed Service Network (MSN) for Children and Young People with Cancer. As a result cancer services for Children and Young people in Scotland are now delivered as a single cohesive service through working of MSN.

Paediatric Haematology is provided by 5 Consultant Haematologists, and there are a further three full time clinical Paediatric oncologists caring for children with solid tumours and brain tumours from the West of Scotland and beyond. The Royal Hospital for Children Oncology service also looks after patients from other principle treatment centres who are referred to Glasgow as per agreed pathways of MSN, or as required for consideration for Early Phase trials.

Radiotherapy facilities are available at the nearby Beatson West of Scotland Cancer Centre and two dedicated Consultant Clinical Oncologists support this service.

Support services available through the Paediatric ECMC centre:

Paediatric National Stem Cell Transplant Unit
Apheresis service provided by the West of Scotland Blood Transfusion Service; this unit is supported by specialist in-house Paediatric Renal, Respiratory, Cardiology, Gastroenterology and Endocrinology Consultants
Radiology Department which has ultrasound, CT and new MRI scanning facilities alongside nuclear medicine; there is also access to interventional radiology
Targeted radio-nucleotide suite for children in the United Kingdom
Histopathology service provided by 5 Paediatric pathologists
Medical Genetics on site with a dedicated cancer genetics service
Paediatric Clinical trials unit staffed by 1 Clinical Trial Co-ordinator, 3 Data Managers and 2 dedicated Research Nurses for early phase trials
Dedicated pharmacist within the centre with lead responsibility for the conduct of early phase trials
A dedicated Teenage Cancer Trust (TCT) unit for teenagers (13 to16 years) & young adults (16 to 25 years) provides a separate, age specific, space both in the Royal Hospital for Children and the Beatson West of Scotland Cancer Centre. Each unit has its own staff trained to look after the specific needs of this group of patients. There is a dedicated TCT support worker who acts as a befriender and information resource for teenagers and their families.
“Home from Home” facilities available on the campus of the Royal Hospital for Children for families travelling long distances for treatment. This service provides brand new, family orientated accommodation which allows whole families to travel and stay while their children are having complex or innovative therapies. Families are housed in a series of apartments which can be configured to their needs and allows them to stay in Glasgow without the expense of dining out, laundry and travel. Within the new house there is also a large social area that allows families to provide informal support to one another.
Prior to discharge follow up arrangements are discussed with the patient their family and additional support is provided the Paediatric Oncology Outreach Nursing service (POON; 3 in Glasgow). Patients and families are also supported by an oncology specific psychology team, CLIC Sergeant service and outreach nurses including and end of life palliative care team.

Case Study

Case Studies

CUBIC - A Phase I/II study of the CXCR2 inhibitor, AZD5069, in combination with Durvalumab (MEDI4736), in patients with advanced Hepatocellular Carcinoma (HCC)

HCC is one of the most common cancers worldwide and the third commonest cause of cancer deaths. HCC complicates chronic liver disease, the incidence of which is increasing dramatically in the UK, attributed to viral hepatitis, alcohol excess, obesity and type II diabetes - related liver disease. Most patients will present with inoperable disease and will ultimately develop disease that is not accessible to loco-regional therapies, and who will then be candidates for systemic anti-cancer therapy.

Tyrosine kinase inhibitors have modest benefits as either first- or second-line therapy in advanced HCC. Inhibition of the immune checkpoint interaction between PD-1 and PD-L1 has promising activity in patients with advanced HCC, but does not improve overall survival as monotherapy. More recently, the combination of bevacizumab and atezolizumab has demonstrated an improved progression-free and overall survival. Nevertheless, survival remains disappointing and novel therapies are needed for this unmet medical need.

Pre-clinical studies in Glasgow and Newcastle suggest that inhibiting neutrophil accumulation in chronic liver disease or targeting their tumour-promoting activities may offer therapeutic opportunities. The primary immune function of CXCR2, the receptor for a number of human chemokines, is the regulation of neutrophil migration and it also regulates the migration of myeloid—derived suppressor cells (MDSCs). In pre-clinical studies, CXCR2 inhibition reduces liver tumour burden and tumour score in vivo and synergises with anti-PD-1 inhibition to prolong survival.

We hypothesise that AZD5069, by inhibiting CXCR2 and, therefore, depleting MDSCs and neutrophils in the liver tumour microenvironment, can enhance the anti-tumour efficacy of PD-L1 pathway antibodies, leading to improved overall survival. Based on these studies we are initiating CUBIC, a multi-centre, open-label, phase I/II study funded by CR-UK, to determine the recommended phase II dose of AZD5069 in combination with Durvalumab in patients with advanced HCC and to determine the anti-tumour efficacy of this combination in patients with advanced disease.

The dose escalation part will use a keyboard design with a target (dose-limiting) toxicity rate of 30% and an acceptable toxicity range of 25 – 35%. After the recommended phase II dose has been identified, an additional cohort of patients will be recruited to determine the anti-tumour efficacy of this combination in patients with advanced HCC using a Simon’s two-stage design.

Exploratory endpoints: pharmacodynamic studies in blood, pre- and on-treatment biopsies of tumour and of non-malignant liver, and will include biomarkers of CXCR2 Inhibition and proof of mechanism biomarkers. Predictive biomarker studies (blood, tumour) include biomarkers of the CXCR2/PD(L)1/immune axis, CXCR2-regulated signal transduction pathways in HCC, biomarkers of proliferation, and tumour mutational status to predict for response and provide insight into the potential mechanisms involved in immune responsiveness or evasion.

This study exemplifies our approach to discover and develop new therapeutics by manipulating the immune system to treat cancer, including by combining immunotherapies with other targeted therapies. The study is scientifically driven, arising from our own laboratory programmes and those of our collaborators, and developed in partnership with pharmaceutical industry collaborators. The study is coordinated by the CR-UK Glasgow Clinical Trials Unit and will recruit patients from 9 ECMCs in the UK. We will maximise the value of the biological and clinical data in tumour and liquid biomarker studies in collaborating laboratories across 5 institutions including the Glasgow Translational Pharmacology Laboratory (ECMC funded) and in the Glasgow Precision Oncology Lab

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Scientific & Operational Team

Operational Team