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.”
A new £10m grant from Cancer Research UK will ensure that adults and children with cancer continue to benefit from world-class clinical trials led by the University of Birmingham.
The news has been hailed as a ‘major boost for patients’ by both clinicians and cancer survivors.
The Cancer Research UK Clinical Trials Unit (CRCTU) at BHP founder-member the University of Birmingham has already achieved significant progress in the treatment of cancer in the UK and internationally, including establishing new standards of treatment for the rare bone and soft tissue cancer, Ewing Sarcoma.
Scientists at the centre have also transformed the management of some types of prostate cancer and introduced treatment innovations for patients with blood cancers.
The new grant will allow researchers working on more than 100 national and international trials to continue developing safe and effective treatments as well as new tests for cancer over the next five years.
Professor Pamela Kearns, Director of the University of Birmingham-based CRCTU unit and children’s cancer expert, said:
“The renewal of funding for cancer trials in Birmingham is a major boost for our research here and we are delighted to continue working with research teams and patients to find new solutions in cancer care. Our clinical research enables us to translate discoveries from the lab and accelerate the improvement of cancer treatments, giving more patients the best chance of beating their disease.
“As a paediatric oncologist, I am particularly pleased this funding will allow our unique Children’s Cancer Trials Unit at Birmingham to continue to design and run clinical trials to improve the care of children with cancer.
“For example, with support from Cancer Research UK, we are leading International trials for children and young people with difficult to treat cancers like FaR-RMS; a trial testing innovative new treatments for rhabdomyosarcoma and the BEACON 2 trial, testing a range of new combinations of therapies for children and young people with a type of childhood cancer called neuroblastoma, at a stage where they have failed to respond well to standard treatments.”
The Birmingham CRCTU will combine strengths in innovative clinical trial methods with outstanding scientific and clinical expertise nationally and internationally to deliver new clinical trials, across all age groups over the next five years. The CRCTU will work alongside the Birmingham Experimental Cancer Medicine Centre, which is also funded by Cancer Research UK and the National Institute for Health and Care Research on trials to tackle more complex types of cancer and for cancers of unmet need.
Professor David Adams, Head of the College of Medical and Dental Sciences and Pro-Vice-Chancellor at the University of Birmingham said:
“The CRCTU is a jewel in the crown of our research portfolio across the University and I am delighted that with this latest funding we will continue to conduct internationally leading research to find better treatments and tests for cancer.
“Together with the ongoing funding for our Experimental Cancer Medicines Centre, the University is ideally placed to continue advances in cancer research which has a hugely significant role in society today. With unprecedented challenges for our NHS and after the effect that the pandemic has had on waiting lists and access to care, we need more than ever to have quick, effective and safe care for cancer.”
The team coordinates ground-breaking clinical trials across the UK and internationally, as well as regionally through Birmingham Health Partners (BHP) – a strategic alliance between seven higher education and health institutions including the University of Birmingham, University Hospitals Birmingham NHS Foundation Trust and Birmingham Women’s and Children’s NHS Foundation Trust.
Improving outcomes – Francesca’s story
Cancer survivor Francesca Williams was one of 640 patients across Europe to benefit from a trial led by the Birmingham centre that has significantly improved outcomes for children and adults with Ewing Sarcoma.
Diagnosed with a tumour in her rib bone just weeks after her 27th birthday in July 2017, Francesca had 15 sessions of chemotherapy and five weeks of radiotherapy back-to-back over ten months. This was followed by major surgery at Heartlands Hospital in April 2018 to remove the remainder of her tumour and rebuild her chest wall using muscle from her back.
Despite going through medically induced menopause and having no time to store any eggs for fertility treatment, Francesca is expecting her first baby in July.
“I feel so lucky to have been part of the trial,” said Francesca, a 32-year-old English teacher who now lives in Austria.
“The worst thing for me was thinking I wouldn’t be able to have children so to find out I was pregnant last year was incredible. I’m really excited about becoming a mum.”
The European-wide trial EE2012, run by the University of Birmingham’s Cancer Research Clinical Trials Unit, tested the standard chemotherapy treatment plan against a new experimental treatment plan in children and adult patients from ten European countries.
The trial – a shorter treatment than the previous standard – found that six per cent more patients were cancer-free after three years, with fewer toxic side-effects. Results were so conclusive that the trial finished early in 2019 and the new treatment adopted as standard across Europe.
“I was very dubious about the trial to begin with but I’m so glad my dad persuaded me to go for it,” said Francesca. “I had no sickness from the chemotherapy so it’s great to hear that the treatment is now being offered as standard. That’s why I feel so passionately about supporting research. Without improvements like this I wouldn’t be here now.
“It’s such a deadly cancer and it is so aggressive, there isn’t the biggest window of opportunity for treatment. It affects a lot of young adults and children who can lose limbs if it’s found in an arm or a leg, but treatment can be successful if it’s caught early enough.”
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.
A £2 million study will see an advanced test used at GP surgeries in the West Midlands to diagnose early-stage ovarian cancer – potentially saving thousands of lives a year.
The project involves BHP members Sandwell and West Birmingham (SWB) NHS Trust and the University of Birmingham collaborating with Walsall Healthcare NHS Trust (WHT) and primary care provider Modality, to offer a blood test called ROMA to patients experiencing symptoms of ovarian cancer.
Signs of the disease include bloating, stomach pain, needing to urinate more often and always feeling full.
If symptoms persist or are severe, frequent or out of the ordinary, women are urged to see their GP where – usually – a CA-125 blood test will be carried out, which has around a 50% detection rate of early-stage cancer.
However, the advanced ROMA test used during this trial at Modality-run GP services in Walsall, Sandwell and West Birmingham, will identify key markers of this particular disease at an earlier stage.
If a patient has tested positive, they will be referred to their local Trust to attend a new one stop clinic where they’ll see a consultant, undergo a specialist scan and then a further consultation where the results will be shared. They will be referred for further treatment if needed.
Speaking about the study, called SONATA (tranSforming Ovarian caNcer diAgnostic paThwAys), Sudha Sundar, Professor of Gynaecological Cancer at the University of Birmingham and Consultant Surgeon at SWB NHS Trust, said: “Ovarian cancer is rare and there is a need to increase the understanding and awareness of the symptoms associated with it among our population and GPs.
“We know that 90% of women diagnosed with ovarian cancer at stage one will survive, but this drops drastically to 15% if it is picked up during stage four.
“Research conducted with my team at the University of Birmingham found out that the ROMA test is significantly better than current tests (CA125 and ultrasound) used in both pre and postmenopausal women*.
“A previous study had found that the ROMA test detects up to 20% more early-stage cancers than the current test which only picks up 50% of early-stage cancers**. We are putting this research into practice by carrying out this trial.”
“With Modality-run GP surgeries trialling the ROMA test we will be able to establish if it is acceptable to patients and clinicians. By testing many samples across two large laboratories, we will be able to confirm whether the ROMA test has a higher chance of detecting this cancer earlier than the current CA-125 blood test used and whether implementing this across the NHS will be cost-effective.”
Leading on the project, Dr Aamena Salar, medical director for Modality Partnership Community Services, said: ‘Our aspiration is to transform the care of ovarian cancer by earlier detection and better outcomes for our patients.”
Nina Jhita, programme director at Modality, added: “This is true innovation; we (primary care) are delighted to collaborate with key system partners across the West Midlands to really make a difference to the lives of women while demonstrating how this solution can be scaled across the UK.”
The final part of the study will see 41,000 primary care samples sent to the Black Country Pathology Service and South Tyne and Wear laboratories to accurately establish whether using the ROMA test rather than CA125 will be cost effective for the NHS. The results from the study, funded by the NHS Cancer Programme and the Small Business Research Initiative, will be analysed and used to change the way this cancer is diagnosed in the future.
Professor Sundar added: “It’s an exciting study which is a great example of integrated working between all the organisations involved. We are looking forward to finding out the results so that we can change the way this cancer is detected in the future and drastically improve survival rates.”
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.
Patients with an incurable blood cancer – polycythaemia vera (PV) – may respond better to a new drug compared to conventional best treatment, a new clinical trial has found.
The rare cancer results in patients producing too many red blood cells and the drug, Ruxolitinib, has been found to be better at treating PV compared to the best currently available treatment. Researchers at BHP founder member the University of Birmingham – funded by Blood Cancer UK – looked at how well the drug worked in those who don’t respond well to the first line of treatment in a randomised phase-II clinical trial.
In this trial, dubbed MAJIC-PV, 39 different hospitals co-ordinated by Birmingham’s Cancer Research UK Clinical Trials Unit (CRCTU) recruited 180 people with PV. They compared ruxolitinib (a drug that targets JAK2 and is already approved for use in PV but not available in the UK) with currently available therapies. Ruxolitinib led to better control of the disease with normal blood counts and a reduced spleen size.
For the first time ever, using samples from the study, the researchers showed that both controlling the blood count and reducing mutated JAK2 by 50% led to fewer disease related events – and that those patients with reduction in JAK2 mutation lived longer, with lower risk of disease progression.
Professor Pamela Kearns, Director of the CRCTU at the University of Birmingham said: “Working on new treatments for incurable cancers is just the kind of thing that the Birmingham Cancer Research UK Clinical Trials Unit is about. I am really pleased that this important clinical trial has found that ruxolitinib has long-term clinical benefit for the ongoing treatment of patients with PV, and that further trials will be able to identify whether the drug can be used as an effective first line treatment.”
PV belongs to a group of conditions that affect the blood called myeloproliferative neoplasms (MPNs). Recently Tim Jonze from the Guardian and ex-radio one DJ David Hamilton have announced they have this form of blood cancer, raising awareness of this lesser-known disease.
The disease is caused by a mutation in a gene called JAK2 and can cause blood clots. Those living with the disease have a risk of a reduced life expectancy as well as development of more aggressive blood cancers including myelofibrosis and acute leukaemia.
One of the commonly used treatments is a drug called – hydroxycarbamide – but those whose cancer does not respond to this drug have a poor prognosis.
Professor Claire Harrison, consultant haematologist at Guy’s and St Thomas’ NHS Foundation Trust and the trial lead, said: “For some time we have wanted to be able to understand the long-term benefits of a drug such as ruxolitinib for patients with PV. This study shows several important messages about this therapy which will hopefully shortly be available for UK patients. These are that comprehensively controlling the blood count reduces disease related events, and that molecular monitoring of mutation levels may also begin to be important.
“Patient therapy is chosen on an individual basis but options have hitherto been limited for PV patients. We are now studying this drug for newly diagnosed patients in a world-first study MITHRIDATE. I would like to thank all the patients who volunteered to be part of this study, their families, UK research teams, Novartis which provided the drug and Blood Cancer UK which funded the trial infrastructure and the trial management team.
Dr Suzanne Rix, Research Funding Programme Manager at Blood Cancer UK, said: “Blood cancer is the fifth most common cause of cancer in the UK, affecting over a quarter of a million people. There is currently no cure for polycythaemia vera and there are a number of complications that can arise from it, so designing, developing and testing medicines to give patients the best outcome possible is vitally important.
“Blood Cancer UK is committed to funding excellent quality scientific research to ensure we deliver better treatments for blood cancer, faster. This trial is a great example of how collaboration between charities, academia, clinicians and pharmaceutical companies can deliver impactful results.
“Our heartfelt thanks go out to those who took part in the trial, without whom we wouldn’t have been able to collect this vital information and continue to improve the outcomes for people with blood cancer.”
