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New treatment combination may improve outcomes for children with rare cancers

Children who develop neuroblastomas, a rare form of cancer which develops in nerve cells, may benefit from receiving certain anti-tumour drugs as well as chemotherapy, a new trial has found.

The results of the BEACON trial conducted by the Cancer Research UK Clinical Trials Unit (CRCTU) at BHP founder-member the University of Birmingham found that combining anti-angiogenic drugs, which block tumours from forming blood vessels, alongside various chemotherapy drugs led to more young people seeing their tumours shrinking, from 18% in the control group to 26% among those on Bevacizumab.

The findings have been published in the Journal of Clinical Oncology. The trial saw 160 young people aged 1-21, from 43 hospitals in 11 European countries, randomised with half receiving the anti-angiogenic drug called Bevacizumab on top of conventional therapy. The group who received Bevacizumab had an increase in the likelihood of responding to treatment, from 18% among those who only had the established therapy to 26% for those with the additional drug. Patients who received Bevacizumab additionally had better one year progression-free survival rates.

The trial constituted one of many collaborations between the University of Birmingham and European expert groups SIOPEN (International Society of Paediatric Oncology European Neuroblastoma) and ITCC (Innovative therapies for children with cancer).

Simon Gates, Professor of Biostatistics and Clinical Trials at the University of Birmingham and senior lead author of the paper said: “These are very exciting results that hopefully get us closer to finding treatments for children who develop neuroblastomas. Currently, the outcomes are really poor for children who get this horrible cancer and so even seemingly small increases in the chance that a patient is going to be able to shrink their tumours is significant.

“We are delighted that the BEACON trial has helped to shape treatment for children with relapsed and refractory neuroblastoma going forward.”

Dr Lucas Moreno, Head of Paediatric Haematology and Oncology at Vall d’Hebron University Hospital, Barcelona, Spain and Chief Investigator for the study said: “BEACON was a hypothesis-generating trial that has served to identify active regimens that are now being further investigated. We are delighted that the data generated has been incorporated into the current UK Clinical Practice Guidelines and Bevacizumab is incorporated into standard treatment for relapsed neuroblastoma.”

Stem cell therapy for heart attack patients trialled at UHB

A stem cell therapy trial at BHP founder-member University Hospitals Birmingham is having a life-changing effect on heart attack patients, with scans showing almost complete restoration of heart muscle function just weeks after the procedure. 

After a heart attack, around 30% of patients are left with severely damaged and weakened hearts which can, over time, lead to life-threatening heart failure, as the heart is unable to pump the blood around the body properly. The trial therapy aims to prevent this heart failure by regenerating the damaged muscle.

Developed by biotechnology company CellProthera, the therapy involves the application of a person’s own stem cells directly into their heart, through the femoral artery in the leg. The patient’s heart activity is then monitored for six months – at 1, 3 and 6 months – using echocardiography and magnetic resonance imaging (MRI).

66 year old Kim Smith is one of four patients recruited to the trial at UHB and was randomly allocated to the experimental arm of the study, meaning that she received the therapy as treatment following her heart attack. Just two weeks after receiving the therapy, Kim’s heart function had returned to almost normal (55%).

Kim said: “I now feel as though I can actually do what I used to do before. When I had the heart attack, I was worried that I was going to end up being stuck at home all day, but since having the stem cell therapy, psychologically and physically, I just feel so much better.

“I’m so grateful to have had this treatment, and I do hope that the research that they are doing goes forward because I think a lot of people would benefit. That was my reason for doing it in the first place – even if it does nothing for me, it could help someone else.”

So far, approximately 50 patients from the UK and France have been recruited to the trial, known as the EXCELLENT (Expanded Cell Endocardial Transplantation) study. The research is currently in its final phase, with results expected later this year.

Dr Sohail Khan, Consultant Interventional Cardiologist and Lead Investigator at UHB for the EXCELLENT study, said: “What we have seen so far is that actually the stem cells do seem to have a dramatic effect in terms of improving heart muscle function.

“Currently, there are few clinical options available that repair and regenerate heart tissue following a heart attack. As a result, the only option for many patients that have suffered a heart attack and developed advanced heart failure, is a fully invasive heart transplant. This is a very serious procedure for the patient, and very costly for society.

“The development of a cell therapy to regenerate cardiac tissue will be transformative for a considerable number of patients globally. A minimally invasive, cell therapy, that uses a patient’s own stem cells, could also considerably reduce treatment costs.”

Matthieu de Kalbermatten, CEO at CellProthera, said: “Bringing the therapy to market as a minimally invasive therapy is vital to tackle, from the root, the harmful effects of heart attacks and improve quality of so many lives.

“The impressive progress of the CellProthera EXCELLENT trial is a testament to the work of our team and our stakeholders. All of the trial sites in the UK and France are committed to admitting and treating the final patients as quickly as possible. In 2024, we will look to start the phase III trial, where we will be recruiting patients from across Europe, with the aim of potential future market authorisation and bringing this vital treatment to all patients.”

NIHR awards £4m to Birmingham Clinical Research Facility to enhance the delivery of research

The Birmingham NIHR Clinical Research Facility (CRF) has been awarded £4 million from the National Institute for Health and Care Research (NIHR).

This funding is part of a total investment of £96 million that has been awarded to NHS organisations across England, to enhance the delivery of research through improving research facilities for patients across the NHS, helping teams to find new ways to prevent and treat diseases.

The Birmingham NIHR CRF is a collaboration between three BHP members – University Hospitals Birmingham NHS Foundation Trust (UHB), Birmingham Women’s and Children’s NHS Foundation Trust (BWC) and the University of Birmingham (UoB).

In Birmingham, new equipment will enable the delivery of innovative health technology services, including a range of cell and gene therapies requiring specialist pharmacy facilities. For example, onsite isolators will support preparation within the research facilities, speeding up the delivery of CAR-T trials for patients with haematology (blood) cancers, as well as trials into cancer vaccines for patients with a variety of solid tumour cancers.

The funding will also provide new laboratory equipment, essential for storing samples from patients recruited to metabolic research studies. This will support researchers with ground breaking work in the prevention, treatment and management of metabolic disease for adults and children across Birmingham.

The bid was led by Jo Gray, NIHR Birmingham Clinical Research Facility Clinical Manager, who said: “This successful bid for equipment and upgrades to our facility is fantastic and will make such a difference to patients and research teams across all partner sites.

“We have ambitious plans in place to upgrade existing equipment, as well as increase our ability to support new research across the sites. New equipment will include a paediatric ‘peapod’, which measures body composition and growth in premature born infants, and biosafety cabinets, which provide an enclosed ventilated space for drug preparation.

“Our portfolio of gastrointestinal (GI) and respiratory studies will also be able to grow with the addition of new endoscopy equipment. One of the key GI trials to benefit will be the INCEPTION clinic for patients with Inflammatory Bowel Disease (IBD). This trial aims to improve diagnosis and prognosis, and make more informed decisions on IBD treatment through biomarker discovery and implementation, by understanding more about how different microbiomes affect gut and oral immune responses.”

Professor Lorraine Harper, NIHR Birmingham Clinical Research Facility Programme Director, added: “We are tremendously proud that our hospitals have been selected for this award from the NIHR to improve the delivery of research in our local population. The award, which builds on existing clinical-academic collaborations facilitated by Birmingham Health Partners, will benefit our adult and paediatric patients, improving their access to new therapies and treatments, which can potentially be life-changing.”

Dr. Jan Idkowiak, NIHR Birmingham Clinical Research Facility Director (BWC), said: “This is very exciting. This award allows us to expand our ability to deliver cutting-edge clinical research beyond the Children’s Hospital, as it will enable us to include pregnant women and their children at the Women’s Hospital. This will be a huge benefit for our patients and will offer great opportunities to develop new therapies.”  

Professor Philip Newsome, Director of the NIHR Birmingham Biomedical Research Centre (BRC), commented: “This is fantastic news for both the CRF and for the organisations that work with them, like the Birmingham BRC. The CRF has been a key partner in delivering many of our experimental research studies, and we collaborate closely on our training, patient and public involvement, and equality, diversity and inclusion programmes too. We are looking forward to continuing working together to deliver patient benefit.”

Cannabinoid-based drug trial for brain tumours launches in Birmingham

A major UK clinical trial of an oral spray containing cannabinoids to treat recurrent glioblastoma has opened in the UK. Funded by The Brain Tumour Charity and coordinated by the Cancer Research UK Clinical Trials Unit at BHP founder-member the University of Birmingham, the three-year phase II trial  will investigate whether combining nabiximols and chemotherapy can help extend the lives of people diagnosed with recurrent glioblastoma.

Anyone interested in this study, which is called ARISTOCRAT, should speak to their medical team first to ensure they are eligible to participate.

It will recruit more than 230 glioblastoma patients at 14 NHS hospitals across England, Scotland and Wales in 2023 including Birmingham, Bristol, Cambridge, Cardiff, Edinburgh, Glasgow, London, Liverpool (Wirral), Manchester, Nottingham, Oxford and Southampton.

Professor Pamela Kearns, Director of the Cancer Research UK Clinical Trials Unit (CRCTU) at the University of Birmingham, which is co-ordinating the trial, said:

“ARISTOCRAT represents a significant step in our journey towards finding safe and effective treatments for the most aggressive brain tumours. By testing innovative combinations of drugs we hope to improve the outcome for this challenging disease.

“We’re immensely proud to be able to bring this trial to patients with the support of the Brain Tumour Charity and thanks to the generosity of all those who gave to the crowdfunding campaign.”

Glioblastoma is the most aggressive form of brain cancer with an average survival of less than 10 months after recurrence.

In 2021, a phase I clinical trial in 27 patients found that nabiximols could be tolerated by patients in combination with chemotherapy, and has the potential to extend the lives of those with recurrent glioblastoma.

Should the trial prove successful, experts hope that nabiximols could represent a new, promising addition to NHS treatment for glioblastoma patients since temozolomide chemotherapy in 2007.

In August 2021, a fundraising appeal by The Brain Tumour Charity, backed by Olympic champion Tom Daley, raised the £450,000 needed for this phase II trial in just three months, and Jazz Pharmaceuticals has generously agreed to provide nabiximols and matched placebo free-of-charge to patients on the ARISTOCRAT trial.

Participants will self-administer nabiximols or a placebo spray and will undergo regular follow-ups with the clinical trial team, including blood tests and MRI scans. This will also be one of the first trials to integrate with The Brain Tumour Charity’s app BRIAN.

Principal Investigator, Professor Susan Short, Professor of Clinical Oncology and Neuro-Oncology at the University of Leeds, said:

“We are very excited to open this trial here in Leeds and very much look forward to running the study which will tell us whether cannabinoid- based drugs could help treat the most aggressive form of brain tumour.

“The treatment of glioblastomas is extremely challenging. Even with surgery, radiotherapy and chemotherapy, nearly all of these brain tumours re-grow within a year, and unfortunately there are very few options for patients once this occurs.

“Cannabinoid-based drugs have well-described effects in the brain and there has been a lot of interest in their use across different cancers for a long time now. Glioblastomas have receptors to cannabinoids on their cell surface, and laboratory studies on glioblastoma cells have shown these drugs may slow tumour growth and work particularly well when used with temozolomide.

“We now have the opportunity to take these laboratory results, and those from the phase I trial and investigate whether this drug could help glioblastoma patients live longer in this first-of-a-kind randomised clinical trial.”

How can I take part in the trial?

Your treating oncologist will be aware of the study if it is open in your hospital or can refer you to a treating centre if necessary. Please speak to your treatment team about eligibility for the trial.

For more information visit the ARISTOCRAT web page on the Cancer Research UK Clinical Trials Unit website. 

UHB launches mRNA cancer vaccine trial for colorectal cancer

BHP founder-members University Hospitals Birmingham NHS Foundation Trust (UHB) has become the UK’s first site to launch the BioNTech Messenger RNA (mRNA) cancer vaccines trial which aims to recruit 10,000 people across the UK.

Launching within the NIHR Clinical Research Facility (CRF) at Queen Elizabeth Hospital Birmingham, mRNA vaccines are one of the most exciting experimental developments to emerge from the COVID-19 pandemic – with strong indications that they could become powerful anti-cancer treatments.

Traditionally, vaccines use dead or weakened viruses to stimulate the immune system into recognising or creating harmless antibodies, so when exposed to the real virus, the body is better placed to fend off an overwhelming infection. mRNA is a genetic material that copies instructions found in DNA, using them to make proteins that carry out functions in the body.

Efficiency and speed are part of the appeal of mRNA vaccines. The manufacture of traditional inactivated virus vaccines takes months as scientists are required to grow these on a huge scale, inactivate the virus, and then formulate it to administer in the general population. mRNA vaccine manufacture only requires the right sequence of genetic instructions.

At UHB, this mRNA trial aims to recruit patients with high-risk stage II and stage III colorectal cancers where there is no standard of care treatment to offer the patient following surgery. Each mRNA vaccine delivered will be personalised to the individual patient.

Around 42,900 people are diagnosed with colorectal cancers in the UK each year. It is the 4th most common cancer in the UK. In Birmingham and Solihull alone, almost 700 people are diagnosed with a colorectal cancer each year.

Dr Victoria Kunene, Consultant Oncologist and Principal Investigator for the trial at UHB, said: “I am really very excited that we have been able to lead the way in setting up this arm of the trial, and am looking forward to being part of the wider vaccine program at UHB.

“We are proud to have an impressive team aptly capable of safely delivering these studies here in the West Midlands, and it is a real pleasure to be part of this transformational trial.”

Prof Simon Ball, Chief Medical Officer, said: “A diagnosis of cancer is devastating for patients and their families; this trial represents a monumental step forward in providing not just hope, but a real promise of delivering better outcomes for patients with colorectal cancer, for whom there is not always a standard of care treatment available following surgery.

“Our research teams, supported by the NIHR, have a proven, distinguished track record in delivering vital trials that make significant contributions to medical and scientific discovery with the patient at the very heart; we’re immensely proud to be able to play a strong part in this here in the West Midlands.”

Participants randomised to receive the study treatment will receive 15 treatments of over one year, followed up for at least 36 months. The treatment is, in essence, a personalised medicine for post-operative patients with high-risk stage II/III colorectal cancer, for whom there is no standard of care treatment and involves the development and testing of an individualised cancer treatment called RO7198457.

UHB is the first site open for this trial – a multi-site, open-label, Phase II, randomized, controlled trial to compare the efficacy of RO7198457, versus watchful waiting in resected, Stage II (high risk) and Stage III colorectal cancer patients who are ctDNA positive following resection.

‘Individualised’ means that the treatment is made individually for each participant according to their unique cancer. This is then tested for mutations which create a unique fingerprint. The goal of an individualised cancer treatment approach is to help train the immune system to recognise and attack cancer cells.

Participants who are randomised to the observation group will be followed up for at least 48 months and visit the research site every three months. Care is provided to ensure safety during trial participation, including an informed consenting process, regular follow up where biomarkers and all reported outcomes are collected and analysed.

‘Vein-on-a-chip’ could help scientists study blood clots without animal models

Blood clot researchers could benefit from a new device that mimics a human vein, replacing the need for animals for some studies.

The vein-on-a-chip model has been developed by scientists at BHP founder-member the University of Birmingham, and can be used in experiments to understand mechanisms of blood clot formation in conditions such as deep vein thrombosis (DVT).

DVT is the development of blood clots in veins, usually in the legs. It is a serious condition because the clot can detach and travel to the lungs, where it may block blood vessels, causing breathing difficulties that prove be fatal. DVT is the third most common cardiovascular disease after myocardial infarction and stroke, with tens of thousands of people in the UK developing this condition every year. Mechanisms of deep vein thrombosis require further research to improve clinicians’ understanding and ability to treat or prevent the condition.

The new device, described in a recent paper published in Frontiers in Cardiovascular Medicine, is a tiny channel, which includes structures called valves that ensure the correct direction of blood flow.

UoB researchers Dr Alexander Brill from the Institute of Cardiovascular Sciences, together with Drs Daniele Vigolo and Alessio Alexiadis from the School of Chemical Engineering, led the development of the new device.

Dr Brill said: “The device is more advanced than previous models because the valves can open and close, mimicking the mechanism seen in a real vein. It also contains a single layer of cells, called endothelial cells, covering the inside of the vessel. These two advances make this vein-on-a-chip a realistic alternative to using animal models in research that focuses on how blood clots form. It is biologically reflective of a real vein, and it also recapitulates blood flow in a life-like manner.

“Organ-on-a-chip devices, such as ours, are not only created to help researchers move away from the need for animal models, but they also advance our understanding of biology as they are more closely representative of how the human body works.

“The principles of the 3Rs – to replace, reduce and refine the use of animals in research – are embedded in national and international legislation and regulations on the use of animals in scientific procedures. But there is always more that can be done. Innovations such as the new device created for use in thrombosis research are a step in the right direction.”

This research was funded by the NC3R, British Heart Foundation and Wellcome.