Exclusive Interview: NCI Director Dr. Ned Sharpless Discusses the Future of Cancer Clinical Trials

Exclusive Interview: NCI Director Dr. Ned Sharpless Discusses the Future of Cancer Clinical Trials

Clifford A. Hudis, MD, FACP, FASCO

@CliffordHudis
Mar 26, 2019

Editor’s note: Dr. Hudis hosts the ASCO in Action Podcast, which focuses on policy and practice issues affecting providers and patients. An excerpt of a recent episode is shared below; it has been edited for length and clarity. Listen to the full podcast online or through iTunes or Google Play.

CH: I am delighted to have as my guest Norman E. "Ned" Sharpless, MD, the director of the National Cancer Institute. We have a lot to discuss, but before we get to our planned topics, I have to jump ahead and start with the president's State of the Union address, when President Trump mentioned that he wants to see $500 million appropriated for childhood cancers over the next decade. Can you talk a little bit about how you expect that to play out? What will the NCI be able to do with those new specified funds for pediatric research?

NS: Childhood cancer is an area where the National Cancer Institute has had a long interest and a robust portfolio of research. It is an area where we've made some progress, in terms of mortality, over the last few decades. But you have to say two things about childhood cancer. While progress has been good, and more kids are surviving cancer therapy today than ever, there's still a long way to go. Too many kids are dying of cancer in the United States, and even the kids that we're able to cure have significant lifelong survivorship challenges, in some cases.

The therapy that is curative may leave patients with side effects of surgery and chemotherapy and radiation for the rest of their lives. Better treatments for kids and less toxic treatments for kids are what we are really looking for. With that amount of money, the thing that one could do to most quickly move the needle in childhood cancer (which, as you know, is a collection of less common cancers, even rare cancers) is a more intentional effort at aggregating and using and linking clinical data with molecular data and other sorts of patient data. So that we can really learn from every child with cancer in the United States. So that we can really figure out what's working in certain populations and then disseminate that information as rapidly as possible, without having, in all cases, to rely on slower clinical trial structures that are challenged for certain populations where accrual can be difficult.

I think that is the vision for the president's initiative: with additional funding, to allow for very aggressive, intentional, and organized data linkages and data aggregation so that we can learn from every trial and therefore treat every child's cancer in a better, more effective way.

CH: I think that's great. The pediatric oncology community for years has really led in designing studies that could accrue the majority of children diagnosed with various specific diseases.

That idea of eligibility and the structure of research leads me to ask about the way that you're thinking about modernizing clinical trials. This is something I know you wrote about in JAMA Viewpoint in the last couple of months. You addressed financial pressures, the need to increase overall rates of accrual to the trials, especially representing patients from underserved populations. Can you expand a little bit on that effort and what kind of progress you see as possible in the coming months and years?

NS: I think everything we do successfully in cancer today is, in some ways, the result of a clinical trial. This is clearly one of the most important things the NCI does, in terms of moving basic science into patient care through experimental clinical trials. It's an area where frankly, a lot's changed in the last couple of decades. When I was a wee fellow, the clinical trials apparatus was very different from the way it is today, 20 years later. We need to make sure that we modernize the clinical trials process to keep up with the changes in our understanding of the biology and the new kinds of therapy we have for cancer.

That brings up a bunch of areas where the NCI is really doing a lot of things. So, for example, one of the first problems I noticed when coming to the National Cancer Institute was that the clinical trials infrastructure, the big networks that we have for doing these kinds of trials, were under-resourced, that they had a funding problem, and they were becoming non-competitive with the trials sponsored by industry.

This showed itself in many ways, in accrual fees for patients, or the wait times to get the trial open, or the slow accrual once the trial was open. So we decided we had to invest in the Clinical Trials Network and have been doing that and will be continuing to doing that in a number of ways—through direct funding to attempt something like the National Clinical Trials Network or the NCORP organization, for example, but also by additional funding for biobanks and data aggregation initiatives, targeted clinical trials, etc.

Also, there are some structural problems with the clinical trials that you alluded to. For example, eligibility criteria, I think, hadn't really kept pace with modern clinical trials. ASCO and other groups have played a really important leadership role in identifying what are good eligibility criteria and which ones are not as necessary anymore.

Then, do we have to have the same criteria in all the trials, and be more thoughtful about how those are used as a way to enhance accrual, because often we have superfluous eligibility criteria that can limit accrual.

Increasing accrual by a variety of measures is really important. I think one of the more successful efforts we've had in clinical trials accrual recently has been the NCI MATCH trial, which was able to accrue 6,000 patients at 1,100 sites in the United States, filling a targeted accrual 2 years ahead of schedule. It's the fastest-accruing trial in the history of the NCI.

One of the things MATCH teaches you is that if you have an interesting trial that's written in a nimble way that is open in the community—patients don't have to drive six hours to a cancer center, but can go to a local NCORP site, for example—then those trials will accrue. We can accrue quickly, and we can accrue underserved populations, and we can accrue rare cancers. That framework is more nimble than, say, the large phase III randomized trial run only at cancer centers that we had 10 years ago.

There is still a role for large, randomized, phase III trials. The NCI is not backing away from that, or where we will support those. But I think, as we discussed in the JAMA piece, we really have to be thoughtful about where the NCI needs to be involved with those kinds of trials, compared to which of those should be supported by industry, for example.

CH: It sounds like you're alluding to something I think you and I discussed even when you first got into your current role, which is the identification of those trials that industry should run, essentially, itself, and those trials that the NCI should support as complementary to industry trials. Can you expand on how you see that distinction and where you draw that line?

NS: The thing to know about clinical trials in oncology in the United States right now is most are actually paid for by industry. There's a huge pharmaceutical industry spend on clinical trials, and from my point of view, that's great. The fact that industry is paying for trials to develop therapies for patients with cancer—that's less money the NCI has to spend on those same questions. So, we think that's a wonderful development and healthy for cancer research.

It's important to say that we do a lot of work with industry—it's not just either/or. Many of our trials, through these agreement processes called CRADAs, allow us to do trials with pharma sponsors and use their compounds in our trials. That's a real boon to our research effort, as well. But there are certain kinds of trials that are very important where we really want to know the answer, but they're a bad fit for what industry is going to fund.

I think the real question we have to ask is, if our budget is limited and finite, what are the trials that the NCI really should do and lead on?

CH: Yes, and I think one of the points there is we need to conduct trials as efficiently as possible, getting the most so-called bang for the buck. You alluded to the fact that the NCI, along with ASCO, has been working on making trials essentially more efficient by making them more representative of the actual cancer population we end up treating.

A specific area of focus for us at ASCO, in this collaboration and also in our TAPUR Study, has been driving the eligibility age down below 18. My understanding is that this is something that you're adopting as a recommendation across the NCI, as well. How broad and how quickly do you expect to see this implemented?

NS: We have a number of efforts related to these barriers to accrual—you mentioned age as one of them, and other sorts of exclusion criteria. We've looked deeply and thought about this sort of care across the continuum of life, both at age limits on the under 18 side, but also at the older than 65 side, where we see, often, eligibility criteria structured around a maximum age that doesn’t make a lot of sense.

That is one of several topics that we are addressing. As you know, we have a variety of networks and programs, and we fund a variety of kinds of trials. Some are led predominantly by the academic institution. Some are led through NCI networks. We are rolling out these policies, not in a one-shot-fits-all way, but across these networks at different scales. They often require scientific buy-in from the other participants, and you know how that process works.

This is an area, fortunately, where there is a lot of buy-in, where we're not having lengthy debates about whether or not we should do this. Really, the question is how we operationalize it and make it happen as quickly as possible.

Listen to the full podcast online or through iTunes or Google Play, and find the latest news on health policy and ASCO’s advocacy efforts at ASCO in Action.

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