Early Phase Clinical Trials

In the second of our two clinical trials episodes, we talk to Professor Sarah Danson, Sheffield Experimental Cancer Medicine Centre Clinical Lead, to learn more about early phase trials, and how the Charity's funding helps to offer brand new treatments to Weston Park patients.

Transcript

Ruby Osborn: Hello and welcome to the Weston Park Cancer Charity Podcast, bringing you stories about our work, what we do and the people we support. From funding life-saving research to providing practical help and emotional support, it's our job to care in every sense for our patients and their families. I'm Ruby, and last episode we had an introduction to the Cancer Clinical Trials Centre at Weston Park. Today we're going into a little more detail about early phase clinical trials.

Sarah Danson: So I'm Professor Sarah Danson, I am a medical oncologist, a cancer physician. I work half the time for Weston Park Hospital and half the time for the University of Sheffield. I treat patients who’ve got lung cancer, mesothelioma, melanoma, and I'm also involved in getting early phase trials, so that's new drugs and new ways of treating cancer, from the laboratory into the clinic. What we can't do is rely on gut feelings about drugs, you know, thinking this makes sense and saying, well if it worked in one patient then it might work in you. We need to get the evidence there so that we're giving people the best treatments that are available. People with cancer only have a limited amount of time sometimes and so you've got to be making the most of that time for treatment, so assessing things in a clinical trial means that it's done in a very rigorous way, it's examined and it's monitored as closely as possible. And so those results will then be something that we can sit down and analyse and help other researchers as well, so clinical trials are the best way for us to improve cancer treatments. 

An early phase clinical trial can really be from the first time that a drug’s being tested in a human all the way up to it going into standard of care practise. We divide these into phase one and phase two studies. So in phase one, you're trying to find the right dose of the drug, or the right combination of drugs, or drugs and other treatments, to give to someone. So you start off low and monitor patients very carefully, look for any side effects and try and treat those, and try and find what dose you can give to patients safely, and you'll take that dose and then look at it further in a phase two study. And so that's when you try and get more information about how the treatment works, so you might try and work out what tumour types to give it in, or if there are any things in the tumour that make it more likely for that drug to work. So it's really, phase one and phase two early phase trials are trying to find out more about the drugs and try and make them work most effectively for patients before we then take them into bigger studies and hopefully change practice and improve practice.

Ruby: What is the experience of being in an early phase clinical trial?

Sarah: If we’ve got an early phase trial open then we let the other doctors know and all the other specialists involved in their care that we may have a treatment option available for their patients. And if that’s something that they think their patient’s going to be interested in pursuing then their own team will then approach the patient and say would you like to hear more, at which point they’ll be give further information about that, and if they still think that they're interested then they'll be referred to the early phase clinic. We'd encourage everybody to feel that that's part of their normal consultation, to be able to ask, you know, is there a clinical trial that I could go into as part of my treatment.

And if patients are eligible that they may benefit from this study then they'll start what we call the screening process, so that might involve scans, blood tests, checking how your heart works. So you go through this screening process which takes a few weeks and if at the end of that everything looks like it’s best option for you, then you go into the clinical trial. So you start the treatment, be monitored closely, we try and do as many of these as possible as an outpatient rather than admitting people, but you might have a long day at the hospital where you have the drug first thing in the morning and then you’re monitored carefully, blood pressure, temperature, possibly ECGs to look at how your heart’s working, blood tests, and then hopefully can go home later that day.

And then depending on how likely we think it is that side effects may happen and how much information we’re trying to get about drug depends on when you come back again. So sometimes people do end up coming daily to be assessed, sometimes it's weekly, sometimes it's monthly. But we would make all of that very clear before we put a patient into a clinical trial.

And then when we've given them an appreciable amount of the treatment, so usually at least two months of the treatment, we do scans. So we have our scans that we've done before they started treatment and then we’d repeat the scans again after that time and we see how they're actually doing. If the cancer continues to grow despite the treatment then it’s no longer in their best interests to continue with that, but if their cancer’s actually responding to the treatment that we would say, right okay, if you’re tolerating this alright then let's carry on.

There’s more uncertainty being in an early phase trial in that we don't necessarily know all the side effects that might come, but actually we do this in a very safe way, that's the point of starting with the lower dose. We do consent patients very carefully, make sure that they understand if they get any problems whilst they’re on treatment that they should get in touch, and we tell them about the side effects that we think might come but equally say to them there may be things that we haven't seen before. So I know some people come and say, well am I a guinea pig? And we don't think that's the case because we will already have got a lot of idea about the drugs before they even get given to patients, so from the research that we’ve done before the drugs going to the clinic.

Ruby: What are the benefits to patients taking part in an early phase trial?

Sarah: The first thing that people always hope is that they will benefit from it themselves, that their tumour will respond to this treatment, and often this is a treatment that they wouldn't be able to get outside of a clinical trial. So I think we always try to be very realistic, we say, you know, if we think that the odds of people responding are low then we would always be upfront with them, but even if it's a 5 or 10% response rate, then that still one in 20 or one in 10 people that will benefit from it.

I can think of one gentleman who was treated for mesothelioma, so that's cancer of the lining of the lungs after asbestos exposure, and he went on to an early phase clinical trial where we were looking at whether you could add something into the chemotherapy, add another drug into the chemotherapy to make it work for longer, and he actually did incredibly well on that. He had the combination of the standard chemotherapy plus the other drug and then he was able to receive the other drug as a maintenance treatment and he was on that treatment for over two years which he tolerated extremely well. He had to come and see us on two-weekly basis but he thought that that was a fair enough trade-off for the control that that he got over the disease, and he was always very complimentary about what the clinical trial aspect had managed to add to his care. Ultimately his disease did begin to grow again at which point he went on to standard chemotherapy again, but he bought that extra time and also gave us lots more information about new drug.

So yes, their tumour may shrink or their tumour may be contained for longer as a result of going into these trials, but the other thing is that people always want to help others, they want to help their children's generation and their grandchildren's generation, and other people that might come along with the same type of tumour as them, so lots of people do for altruistic reasons to try and give us more information to improve the care that we give to patients with cancer.

Ruby: So how many patients at Weston Park take part in early phase trials?

Sarah: Early phase trials tend to be quite small, it's a small percentage of the total number that go into trials. So our aim is to get 20% of all patients in to a clinical trial, but that might be an early phase trial, a late phase trial, or sometimes it's not a treatment trial, it might be an observational trial or a trial to support their health needs. So we would treat up to 100 patients a year usually in these types of early phase trials.

Ruby: What makes Sheffield a good place to do research?

Sarah: So Sheffield's a great place, it’s a vibrant area, it’s a beautiful area, and the people are absolutely great. But it is not a wealthy area and unfortunately cancer affects those who don't have as much money preferentially compared to those who are more wealthy, so unfortunately we do have lots of cancer in this area and in the region and in Yorkshire as a whole, and therefore we do have a great need. But you could look at it the other way to say, well if you were going to research cancer anywhere then somewhere like Sheffield is exactly where you should be doing it, you can make the most benefit and you can get the most patients in if you open trials and run research in an area such as this.

So Sheffield is one of 18 Experimental Cancer Medicine Centres in the United Kingdom and that means that it's a centre that's been accredited to provide early phase cancer trials, and having that ECMC badge is very very useful in getting trials and in getting funding, and in interacting with drug companies as well who might be considering where to run their research. But it also gives us a network so we do work with those other 17 centres, especially the ones in the north just because of geographical proximity, so if patients don't have an option locally then we can always reach out to our colleagues in these other centres and ask if they've got some clinical research going on that will benefit our patients and they can do the same to us, so it adds something to the care that we give to patients.

You know we've got some really good research going on, we've got some great minds too, so that's the other thing that Sheffield has, is it has the brains behind the research too.

Ruby: How is Weston Park Cancer Charity funding used with the early phase trials that are run at the hospital?

Sarah: So we're very lucky that the Cancer Charity supports us to be able to deliver these types of trials, so we get funding from various sources, but the Weston Park Cancer Charity funding allows us to employ research nurses who’re obviously essential for the face-to-face contact with patients; data managers, so they’re the ones that are making sure that the research that we generate, that the data is of high quality so that we can make decisions about what we do with our research next; we take lots of samples from patients, these might be samples that we’ve already got like tumour samples that have already been taken or new samples such as blood samples, and so we have lab technician support; and also most of these types of trials are drug trials so what we need is pharmacy support as well so the Cancer Charity supports a pharmacy technician to help us dispense those drugs. So all of those things work together to provide the infrastructure that we need to be able to treat patients in these types of trials.

Ruby: It's predicted that in the next year there's going to be a 40% decrease in UK charity medical research spent due to the effects of the pandemic. Why is it important that people keep supporting charities that fund research?

Sarah: Yeah so for cancer, cancer research, charity funding is very important indeed, much more so than in many other areas of research. And we can't stop improving our cancer care because of covid, because of drops in the amount of research that's available, we have to keep on trying to improve things. So yes, I was I would urge anybody who's in two minds about whether to donate or not to still do so, because the researchers are still there and crucially the patients who’ve got a great need are still there as well. Nothing has stopped during lockdown, people have carried on having innovative ideas, researchers have carried on writing papers and putting trial proposals together, and of course cancer hasn't stopped either, patients have carried on developing cancer despite this. So we've got to use the money wisely knowing that there’s the drop in funding, but we must certainly not stop.

Ruby: That was Professor Sarah Danson, clinical lead of the Sheffield Experimental Cancer Medicine Centre. Thank you for listening. If you missed our last episode, give it a listen to find out more about the work of the Cancer Clinical Trials Centre, and if you want to help us enable research like this please visit westonpark.org.uk.

Dean Andrews: Cancer changes everything, but so can we.