The revolutionary ADRRAD trial turns conventional thinking about advanced prostate cancer on its head, attempting to overcome a disease that's considered terminal. Dr Sophie Lutter looks behind the scenes at what makes this such a game-changing enterprise and why it represents the perfect dance between medicine and science.
Together with the Movember Foundation, we established the UK’s first Centres of Excellence for prostate cancer research back in 2014. The aim was to bring science and medicine closer together, and to shorten the time it would take for scientific benefits to reach patients.
One of the major clinical wins from the Belfast-Manchester Movember Centre of Excellence so far is the ADRRAD trial, and the scientific work that underpins, accompanies and weaves through it. This isn’t a win in terms of results – at least not yet. The trial has only just opened to patients. But it’s most definitely a win in terms of game-changing thinking, revolutionary project design and innovative collaboration.
The scientists and doctors behind this project are not just changing the status quo – they’re turning it on its head. Advanced prostate cancer is, and always has been, incurable. Now these researchers are asking whether hitting the cancer with everything we’ve got from the point of diagnosis might help change that.
We don’t know yet whether it will work. It certainly won’t all come out of this first study, which for anyone in the know about how clinical trials work, is a phase I toxicity study. For the rest of us, that means a small-scale trial to be sure that the treatments are safe, and that there’s enough evidence that they’ll be beneficial to take the research to the next stage.
But what’s so exciting about this work is that now scientists are able and willing to look at the problem of advanced prostate cancer without worrying about whether an extortionately expensive new treatment might give a man a precious few more months of life. Instead, they can ask whether they can change the way we use treatments that have already been developed to give a man his life back.
Where ADRRAD differs is in the revolutionary way that the science and medicine are inextricably linked behind the scenes
The STAMPEDE trial, which hit headlines at the end of last year after the unprecedented success of the docetaxel arm of this major trial, has a similar approach – hit it early, hit it hard, and get ready for the big win.
But where ADRRAD differs is in the revolutionary way that the science and medicine are inextricably linked behind the scenes of this clinical trial. Usually, the two work together but in sequence. Scientific experiments suggest that something is worth testing in the clinic. The clinical trial happens, and any unusual findings are then tested again in the lab to try to explain them. This may then inform a later clinical trial. It’s like a carefully choreographed dance, but where all the dancers are solo acts.
This trial is Strictly Ballroom: the two parts of the study move together seamlessly. At the same time as the clinical trial looks to show overall patient benefit, the scientists experiment with cells and mice for detailed insights into exactly how and why the trial is or isn’t working, why this might vary from one patient to another, and whether this can suggest improvements to the trial protocol as they develop the next phase. Might tweaks to the order, timing, duration or dosage of treatment, for example, make a difference?
This type of personal approach will turn cancer treatment from a blunt force to a precise art
They’re also asking what blood samples from men taking part in the trial can tell them about individual characteristics of each man’s cancer, and how that might affect how the treatment works for him. This should mean that by the time the researchers are ready to develop the next phase of the trial, they’ll know which men are most likely to benefit from this treatment and who might be better off trying another treatment approach. This type of personal approach will turn cancer treatment from a blunt force to a precise art.
Personally, my favourite thing about this piece of work is all the people and expertise it brings together to make it work. The project is working across two cities, two universities and two hospitals. The clinical trial and some of the lab work is happening at the Northern Ireland Cancer Centre and Queen’s University Belfast, while another part of the lab work happens at the University of Manchester.
We’ve already talked about the magic that can happen when scientists and clinicians work together, but this project also brings prostate cancer experts together with lung cancer experts to piggy-back on successes in that area for the benefit of men with prostate cancer.
This trial show what can happen when charities, industry and academic institutions work together
And finally, the scope and ambition of this trial show what can happen when charities, industry and academic institutions work together to bring benefits to patients. No individual, institution or organisation involved in this project would be able to do any of it without the others.
It’s going to take more than a single hand to win this life-and-death poker game with prostate cancer. But this is just one of the cards we’ll be playing over the next 10 years as we work towards a world where men outlive their cancer, and no-one experiences side effects from a treatment that ultimately isn’t going to benefit them.