Clinical Trial Spotlight

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Here we feature clinical trials and translational research in cancer happening around the UK. You’ll find the latest information and evidence and hear from the research nurses, practitioners and researchers working on them.

The National Lung MATRIX trial (MATRIX) has been renewed for another 3 years and in October 2018, marked the recruitment of its 250th patient. 

To celebrate, we spoke to Gemma Murphy and Krishna Patel who run MATRIX at the Cancer Clinical Trials Unit, University College London Hospital (UCLH). Watch the video below to hear about their work on MATRIX, including advice on how they overcome the daily challenges of working on a large multi-arm trial.

Working on the National Lung MATRIX clinical trial

Thanks to the power of research, we now understand that every patient’s cancer is unique, with potentially very different genetic and molecular characteristics. The Stratified Medicine Programme (SMP) is a national, genetic screening programme, the first of its kind in the UK to pre-screen cancer patients’ molecular eligibility for a cancer clinical trial. Excess diagnostic biopsy tissue from patients with advanced lung cancer is screened for specific markers to assess the likelihood of a targeted treatment being effective for each patient. 

SMP1 has paved the way for SMP2. Focussed solely on lung cancer, SMP2 not only uses genetic screening to test lung cancer patients, but also aims to connect them with the National Lung Cancer Matrix trial. MATRIX is the world’s largest precision medicine trial for lung cancer. A phase II study incorporating multiple treatment arms, it consists of over 20 different biomarker-drug combination cohorts and uses a design that allows the trial to adapt and evolve as necessary. New drugs can be included as soon as they become available and others can be quickly removed or replaced if evidence suggests that they aren’t as effective. 

Bladder and urinary tract cancer is the ninth most common cause of cancer death in the UK and accounted for 3% of cancer deaths (around 5,400 people) in 2016. The usual treatment for advanced urinary tract cancer is chemotherapy, followed by a treatment-free period where patients are checked periodically for signs of the cancer returning.

At Cancer Research UK’s Clinical Trials Unit in Glasgow, the phase II ATLANTIS trial is investigating whether treating patients with targeted cancer drugs after chemotherapy will delay the cancer returning and improve patient survival. Not all urinary tract cancers are the same and new drugs may help some people more than others. So, the trial involves analysing a patient’s tumour and looking for mutations in certain genes and proteins. Depending what this analysis shows, patients could go on to receive one of two targeted drugs – either cabozantinib or rucaparib. The team hopes to add more drugs to the trial in the future, providing crucial information about whether precision drugs could improve outcomes for patients with advanced urinary tract cancer.

"ATLANTIS is a great example of providing patients with access to new targeted therapies that they wouldn’t ordinarily have," says Martin MacLeod, a clinical research nurse working on ATLANTIS in the trials unit in Glasgow. "It’s hugely interesting to work on. I think we’ve screened about 9 patients so far and 5 of them have went on to the trial. Nationally 44 patients have gone on to the trial after screening.  I’m closely involved with consenting the patients, helping them to understand what’s involved. After starting on the trial, patients come in every 4 weeks. I screen their blood, check their vital signs, take local bloods and analyse urine samples, checking and discussing lab results with the oncologist and trial pharmacist."
"As it’s a biomarker driven trial, it’s important to remember that the patient may not test positive for the biomarkers you’re looking for and that you communicate this to the patient. I do find, though, that even if this is the case, it opens the patient’s mind to other possible trials and treatment options."

The ATLANTIS trial has been running since 2016 and aims to recruit 188 patients by 2020, with 15 out of 24 recruitment sites – including Glasgow – now open. 

To find out more about the ATLANTIS trial design and patient eligibility criteria, visit the ATLANTIS trial page on the Clinical Trials Database.

"The personalised breast cancer project is absolutely unique – for breast cancer, it is the equivalent of going to the moon." Professor Carlos Caldas 

In the 1970s, just 4 in 10 women with breast cancer survived their disease beyond 10 years. This number has doubled so that now, around 8 in 10 women will survive their disease for at least 10 years. 

But breast cancer is still the most common cancer for women in the UK and, despite our incredible progress, around 11,400 people die from the disease in the UK every year. Professor Carlos Caldas, based at the CRUK Cambridge Institute, is determined to change this. In 2012, Professor Caldas and his team made the landmark discovery that breast cancer is not just one disease – but ten. Not only are these diseases very different in terms of their genetics, they also respond differently to treatments, meaning patients may have varied outcomes.

This discovery was the result of a project called METABRIC, through which the team collected and compared more than 2,000 breast cancer samples. They also discovered faults in 40 genes that can cause breast cancer to develop – only a fraction of which were previously known to be involved in breast cancer development. This information is crucial, providing new insight into how breast cancer develops, and why some patients respond well to certain treatments while others don’t.  
Professor Caldas is taking his findings to the next level, running the five-year Personalised Breast Cancer Project (PBCP) to match patients to the best treatment for their cancer. 2,500 women treated at the Cambridge Breast Cancer Unit will have their tumour DNA analysed, which will be recorded alongside their response to treatment. The team will be able to analyse the entire genetic code of each person’s tumour, which is a huge technological step forward – their previous study could only analyse part of this DNA. Importantly, this will allow the team to see every genetic fault behind each of the ten tumour types, providing unprecedented insight into what caused each patient’s disease to develop. 

"The Personalised Breast Cancer Project is truly ground-breaking. By sequencing the entire tumour genome of people with breast cancer in our clinic and integrating this data with other observations, we will assign patients to optimal therapy, changing the way we treat breast cancer forever," says Professor Richard Gilbertson, Director of the CRUK Cambridge Centre. 

This information will feed into an unparalleled database of genetic and clinical information to be used by doctors and researchers around the world, to ensure people with breast cancer are accurately diagnosed and matched to the best treatment for them. But the reach of this research goes beyond breast cancer. Professor Caldas’ insights could be applied to other types of cancer, ensuring people receive treatment tailored for their disease – and giving them the best chance of beating their cancer. 

Find out more about the iKnife surgical technology and how it’s being used in the REI-EXCISE trial for patients with breast cancer. 

Learn more about iKnife and REI-EXCISE on the Clinical Trials Database.  

Since 2005, we’ve been funding a trial called STAMPEDE, led by Professor Nick James at the University of Birmingham. The multi-arm trial aims to find the best treatment for newly diagnosed, advanced prostate cancer by combining standard hormone therapy with a range of existing treatments to try to find the combination that is most effective at beating the disease before it becomes resistant.

Initial results from STAMPEDE have already changed clinical practice, after showing giving the chemotherapy drug docetaxel at an earlier stage improves survival. Then, in 2017, results from the trial showed that combining the drug abiraterone with other hormone therapies at the start of treatment dramatically improves five-year survival by an incredible 37%. Abiraterone, which was developed by Cancer Research UK-funded researchers in the 1990s, is a testosterone-blocker that works in a different way to standard hormone therapy and these results have already led to a change in how men are treated. Further results released in October 2018 showed that, for men whose prostate cancer has spread to elsewhere in the body, survival can be substantially improved by providing additional radiotherapy. 

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