Colorectal cancer screening and the EORTC SPECTA initiative

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Published: 26 Jun 2014
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Dr Sabine Tejpar - University of Leuven, Leuven, Belgium

Dr Tejpar talks to ecancertv at the WIN Symposium 2014 about the EORTC SPECTA (Screening Patients for Efficient Clinical Trial Access) initiative, focusing on the colorectal cancer screening platform.

What we started at the EORTC now, a good year ago, is what we call the SPECTA platforms which are happening in different disease types so maybe I’ll just talk about the colon as one I’m very involved in and as an example but it’s also in brain tumours, melanoma, lung etc. So the point really is that today you have all these new molecular classifications going on, you know that no drug is going to work in all patients, this is a given. So you know that when you develop your drugs, either from pharma or academic, you need to take into account all these stratifications. The stratifications are really difficult to do, they’re complex technically, they’re probably beyond the remit of a single institution, probably even a country. If you want to offer that to your patients it would be really hard to get that organised on a national level. So to bring down all those barriers the point was let’s just all do it together, let’s put it into one big pot. By centralising efforts and money, funding, we are able to offer for any country, any tumour that gets diagnosed, all this state of the art profiling and doing it just once. But then everybody can profit from it in the sense that you have a specific clinical trial from one pharmaceutical company wanting to look for patient x, y, z, can come in, look for it. Another company looking for another profile on the same patient population can look for it. So we’re just trying to mutualise this, make it much more efficient, to decrease the time it takes to otherwise set up these really difficult efforts. If you don’t set up these efforts they just won’t happen. So these are platforms really meant to mutualise to increase efficacy. That’s fun because we get to pour in our science and then you just see it happen.

So this is helping to stratify and choose your patients in colorectal cancer?

On the science part we know that there are features that need to be taken into account. The fun thing there is that we can dictate which are the features we think are important to measure and that means we can go very far, very complex, because some of our frustrations otherwise is that even within clinical trials only very basic features get measured. We go, “It’s not enough! You need to go further than that.” So here we can really say, “OK, we’re just going to measure tonnes of complicated features.” So that input is really fun for us. The other part, then, is indeed that this makes it attractive for pharma and academic trials to come in and say, “OK, you’ve given me the resource now with, let’s say, 100 live patients with this very rare feature. Let’s just go and cherry pick them and test my drug in them.” So it’s a live platform of annotated patients. That’s the other part where our frustrations are decreased, it’s the fact that we can run these trials now. Before we had cool ideas but it seemed like an insurmountable mountain to set it up. It’s just the logistic part is taken care of, that’s it.

What, specifically, is being measured?

Colon is fun because there have been a lot of changes in the last year. If you remember for breast and for colon and we’re talking just about AML here in the session, just before today, so there has been sub-stratifications going on for many diseases. Breast you would never treat them in the same way. So colon was really lacking so part of also our academic work, again in international consortia, was to get a real biological sub-classification going for colon. Intrinsically different biological features that we know those colon tumours, whatever you given them, it doesn’t matter, from the beginning they’re different. This, for example, is something we presented at ASCO this year so it’s just very fresh data, it still needs to be published. But you can already put it into your platform, so you know that the next drug trial will take into account those features. These are hundreds of mutations, full gene expression, so very complex features which again you can do centrally but you can’t expect everybody to set this up in their own lab continuously or every drug trial again do that, it just would be impossible.

So how do researchers actually access the information?

It’s very open, so you provide patients, materials. So the point is you have a live patient who one day may enter a trial, so he’s fit enough to enter a trial, he has metastatic disease for example. So you enter your patients, this material is sent to central labs which can rotate. There’s not a fixed thing so if you have a really cool facility or really cool idea you can get part of the material and run your tests on it. The return to the clinician, then, who entered the patient is that he has all this molecular data comes back to him so he knows now a lot of things about his patient that comes straight back to him. He can use that for his own approach, potentially, if he wants to try out something based on one of these features. He has this feedback of these omics on his patient coming straight to him but, on the other hand, the patient goes into a database, a database of live patients which we update every six months to know how they’re doing. That’s where you can come in and mine for a trial. You say, “OK, I want ten live patients with this feature at that stage of the disease.” So we do hope that those patients will actually get exposed to clinical trials. So that’s the win-win for the patient, win-win for the clinician and us basically just facilitating this.

Who do people contact?

There’s a website, there’s folders. If you go to EORTC SPECTA or SPECTAcolor there’s the website so all the contacts are there.

What have been some of the results so far?

In general we’re just setting up, well, we’re actually up and running so I’m not going to say that we have been able to already prove exactly, which is what we want to do, is to prove certain mutations will predict certain drug responses. That may not necessarily even be the case, we know that there are a lot of problems there. That’s not really our aim either; our aim, and I think where our deliverables and where we can be measured at the end of the project, is to know were we able to get good quality molecular sub-typing which is state of the art, including unpublished academic ideas like the ones we’ve discussed today at WIN, have them running in an efficient way on thousands of patients every year and these patients then being used by the community, either the academic community for your own trial or the pharma community for one of their trials. That’s actually our deliverable. Afterwards, does the drug work in the patient, that’s a different question. But it’s really getting more exposure of these patients to the drugs.

What about patient consent?

We get the patients early on in their disease because actually we want to be able to offer them a lot of options while they’re alive. That’s also what we tell them - we are going to be able to provide you with some profiling which is beyond what we could be doing ourselves in our hospital or whatever. There are really only clear advantages to them. What we do make sure is that this material is always treated in an anonymous fashion and the molecular data can’t be linked to any of their features. We also have a process how to handle germline alterations should you find them. So the usual things you have to take care of. Basically it’s completely in the interests of the patient to get to know more about his tumour and they’re quite excited about it, actually, they ask for it.

It’s also important, there are more and more patients aware of this through the media and I’m not talking about SPECTA but just in general about molecular profiling. So they would tend to go out on their own, maybe, and even pay outside companies. We get that, we get patients coming with their full reports. First of all the report you can’t interpret because, in SPECTA at least, what we measure we interpret. The second thing is imagine if a patient were to do that and send his material to two or three sources, he would not have any material any more. So what we try to do is centralise; whatever you do on this material is in one repository. There’s one pathologist that handles the material of that patient and we make sure it’s efficiently handled. That is also in the interests of the patient.

What are the challenges facing this initiative?

Money! Because, as I described it, it’s a facilitating platform but if there’s no end user or no clear benefit for an end user there’s no money coming in. So at the moment we’re fantastically lucky to have charity money and specifically for the colon this is Alliance Boots is sponsoring us. So it’s really they who do all kinds of charity events all over the world just for the SPECTAcolor platform. For each disease we have different charities so at the moment it’s all charity money. Yes, the viability of this all will be the pick-up by society, maybe by even payers, regulators, pharma, whoever. When they get to see the advantage for themselves then it can be something that can be funded. But it’s something you want to set up and keep on running forever, actually. So that’s the challenge.

What do you hope to achieve and what’s the timeframe?

For me the deliverables are to have a live pool of patients that can get queried and where actually all the parties are happy. For example, if a pharma wanted twenty live patients in centres with which they used to work, maybe a phase I trial, a difficult trial, that we can provide those. But for me also what the big challenge is is that the omics data that we do is of good quality. So that’s a big thing, quality assurance, so we have in this platform a lot of quality assurance going on, we talk to the regulators, we have the European Society of Oncology - it's integrated here so we make sure that the quality has to be really high. If we can find a way to deliver harmonious quality over time for many complex markers and have this open to new people and new ideas that want to come in with a new marker and still we can keep on providing a well-oiled machine, that would be the deliverable for me. If we can manage that then I think we have what we wanted.