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 27^th 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.”

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.”

Children with some solid tumours may benefit from receiving a combination of inhibitor drugs, according to interim results of research presented at the American Association of Cancer Research’s Annual Meeting 2023, held April 14-19.

The ongoing research being conducted by an international team including the University of Birmingham suggests that a combination of the PARP inhibitor olaparib (Lynparza) and the investigational ATR inhibitor ceralasertib showed clinical benefit in paediatric patients with solid tumours exhibiting DNA replication stress and/or DNA repair deficiencies.

Dr Susanne Gatz, associate clinical professor in pediatric oncology at the Institute of Cancer and Genomic Sciences of the University of Birmingham presented the study.

Dr Gatz said: “To our knowledge, the combination of PARP inhibitors and ATR inhibitors has not been widely investigated in adult tumour types. This is the first proof of principle that the combination is well tolerated and can lead to clinically relevant responses in paediatric cancers.”

AcSé-ESMART is an international European proof-of-concept platform trial intended to match paediatric, adolescent, and young adult patients with relapsed or treatment-refractory cancers with a treatment regimen targeted to their cancer’s mutational profile. Gatz and colleagues, including Birgit Geoerger, MD, PhD, head of the AcSé-ESMART trial, have so far evaluated 15 different treatments, mostly combination strategies, in more than 220 children following mandatory high-throughput genomic profiling of their tumours.

Arm N of AcSé-ESMART is tailored toward patients with malignancies that exhibit defects in DNA replication and damage repair. Impairments in homologous recombination (HR), a type of DNA repair, can sensitize cells to drugs called PARP inhibitors. PARP inhibitors have proven effective against specific adult cancers with HR deficiencies—most notably, mutations in BRCA1 or BRCA2. How to best use PARP inhibitors in paediatric patients where BRCA1/2 mutations are rarely found remains unclear.

Dr Gatz said: “Paediatric cancer cells proliferate rapidly and have some element of replication stress and a dependency on ATR. We think there might be a kind of primary resistance of paediatric cancers to PARP inhibitors and that combination with an ATR inhibitor could potentially overcome that.”

Gatz also explained that paediatric cancers are often driven by complex mechanisms, making it difficult to identify an effective treatment regimen. Single-agent therapies targeting one mutated protein are often insufficient in paediatric patients, necessitating additional research into combination therapies and mechanisms of response.

“So far, it is unclear if the molecular alterations based on which the patients were enrolled in this trial are the sole reasons for response,” Gatz said.

“Further, it may be difficult to identify patterns of response in specific tumour types due to the tumour-agnostic nature of the study. Nevertheless, this study design can give preliminary indications of signals in specific alterations and tumour types and can provide the basis for future clinical trials.”

Gatz and colleagues plan to evaluate biomarkers of response from the raw sequencing data of the enrolled patients, from the expression of key target proteins such as ATM, and from RNA sequencing data.

Gatz noted that these analyses may identify “molecular constellations” indicative of response to olaparib plus ceralasertib.

“There are enormously valuable drugs currently in development and, provided there is a good clinical or preclinical rationale, we need to apply them more creatively to diseases for which the drug is not currently indicated,” Gatz said.

Limitations of this study include a small, non-randomized sample intended primarily as a proof of concept and to determine the optimal dose for study expansion.

The study is as yet unpublished.