Current Landscape of Prostate Cancer Clinical Trials - Alliance Cooperative Group - Michael J. Morris

Michael Morris joins Alicia Morgans for a conversation on the focus of the GU Committee of the Alliance Cooperative Group that is led by Michael Morris. While there is a continued focus on advanced prostate cancer, there is an expected readout on a 12-year study in early disease, the CALGB 90203. CALGB 90203 (Alliance) looked at radical prostatectomy (RP) with or without neoadjuvant chemohormonal therapy (CHT) in men with clinically localized, high-risk prostate cancer (CLHRPC). Dr. Morris describes the Alliance likes to focus on trials that the pharmaceutical companies do not do. Those might involve off-patent drugs, whether those are on the investigational arm or control arm. There are also circumstances where you need to compare one drug with another drug. Or in rare diseases, so for example, we have a germ cell tumor international trial. Which is a rare disease and it's looking at a rare circumstance in that rare disease. The cooperative groups are a blend, both of your traditional academic centers which do a lot of the early phase development and community clinics. He explains that the cooperative studies are far more real-world facing since over half of the investigators are from the community. The cooperative trials are often able to answer definitive clinical questions with a definitive clinical outcome. He also describes the mentoring opportunities for the younger investigators from one academic center working with other investigators from across the county, beyond the same institution. Dr. Morris provides invaluable insight, overall into the Alliance Cooperative Group GU Clinical Trials.  

Biographies:

Michael J. Morris, MD, Medical Oncologist Clinical Director, Genitourinary Medical Oncology Service & Prostate Cancer Section Head, Division of Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center, New York, NY

Alicia Morgans, MD, MPH Associate Professor of Medicine in the Division of Hematology/Oncology at the Northwestern University Feinberg School of Medicine in Chicago, Illinois.

Read the Full Video Transcript

Alicia Morgans: Hi, I am so thrilled to have here with me today, Dr. Michael Morris, who is the Clinical Director and Genitourinary Medical Oncology Service and Prostate Cancer Section Head at the Memorial Sloan Kettering Cancer Institute. So lovely to have you here. Thank you.

Michael Morris: Thank you for having me. 

Alicia Morgans: Of course. So besides your enormous role in prostate cancer at Memorial, you also have many other hats. And one of those hats is running the GU committee in the Alliance Cooperative Group. 

Michael Morris: Correct.

Alicia Morgans: And I would love to hear your take on the current landscape of prostate cancer clinical trials within that cooperative group. Where are we, where are we going, what's that landscape look like?

Michael Morris: Sure. Well, we have a significant portfolio, as we've always had historically in the cooperative groups in advanced disease. And there are across the National Clinical Trials Network, studies looking at advanced disease in terms of AR-directed therapy. There is a PARP inhibitor study as well. But I think that one of the most important things is now, we're going to get some readouts on early disease. There has been a trial that has been percolating for 12 years now. That is CALGB-90203. That study looked at men with high risk, localized prostate cancer and was, men who were going for radical prostatectomy who would be randomized to docetaxel and hormonal therapy and their surgery, versus surgery alone. That trial has read out and will be very very shortly presented. We hope both at AUA and at ASCO. 

And so that should give us the first insight into neoadjuvant therapy. Which is, honestly, where I think many of us who are in the cooperative groups, as well as not, would like to be because many of the contemporary therapies that we have now suggest that they have a lot more potency in terms of at least reducing tumor volume, if not eliminating it. And I think that slowly the groups are moving from a real focus in advanced disease to both getting readouts and new trial designs, both in early disease and in the rising PSA space. And in the castration sensitive space. 

One of the most exciting trials that we have in castration sensitive metastatic disease is an upcoming proposal that we have in cooperation with NRG. So that's our group alliance with NRG. Looking at ADT and an antiandrogen of the physicians’ choice with and without 177Lu-PSMA-617. PSMA radioligands have been something that we've really wanted to have here in the United States, so we have now a registration trial of 177Lu-PSMA-617and that's in post-chemotherapy CRPC. But what we would like to do in the cooperative groups is bring that to see if we can't have a new standard of care in men with metastatic castration sensitive disease. Using that compound and we'll see how that goes. These are big, interesting, and new standard of care, potentially setting clinical trials with real clinical readouts. So we're hoping to get that through.

That's one of the collaborations that I'm really excited about working on. 

Alicia Morgans: Absolutely. So one of the things that I think is most exciting about the cooperative groups, is that you're able to do trials that are large. And you engage the people around the country. It's not a few isolated sites. It's actually often many sites. And I'd love to hear if you can explain to the people listening, what are these cooperative group trials, what do they look like, and how do patients really engage? Because it's easier sometimes than traditional pharmaceutical company studies.

Michael Morris: Yeah. So let's just pick up that last point. What kind of trials do we do? We like to focus on trials that the pharmaceutical companies can't do. So frequently those might involve off-patent drugs, whether those are on the investigational arm or control arm. Or circumstances where you need to compare one drug with another that Pharma might not want to do that. Or in rare diseases, so for example, we have a germ cell tumor international trial. Which is a rare disease and it's looking at a rare circumstance in that rare disease. And the other nice thing about the cooperative groups is that it is a blend, both of your traditional academic centers which do a lot of the early phase development. And so you get a sense from those early phase trials, what an academic population with academics would look like in terms of results, in the cooperative groups, about have the centers are community-based.

So you get a much better sense of how would this drug really perform in a real-life scenario. Outside of the ivory tower of an academic center. So we're often able to answer really definitive clinical questions with a definitive clinical outcome, in a circumstance where either Pharma couldn't afford to do that because this is an NCI taxpayer-funded studies or has no interest in doing that. We do though, have a real interest in molecularly driven smaller studies as well. And this is an expanding part of the portfolio that NCI has really encouraged us to do. So, to compete in an arena that in the past Pharma has done very well. But also, to focus on things that perhaps Pharma doesn't have an interest in.

Again, for the reasons that I just discussed, but are perhaps Phase 2 studies with biologic endpoints that can inform then a Phase 3 trial. So right now in the alliance, about half the portfolio is in an earlier phase than Phase 3. 

Alicia Morgans: Wonderful. Again, giving opportunities to investigators to really define where we go next, in Phase 3 and opportunities for patients, not just in large academic centers, but in the smaller community sites to have access to therapies earlier.

Michael Morris: Absolutely. And I think that the other thing is that it really is an opportunity for junior people to get their ideas into the Phase 3 arena. Which otherwise, may not be an opportunity that Pharma would provide. So it's mentorship for our junior faculty, it's an opportunity for them to take an idea that they may have started within their institution, and then can deploy that on a national and potentially an international scale. So if you look within the GU committee, for example, we have a number of concepts. Darren Feldman is leading a really definitive exciting germ cell tumor trial. You have an opportunity to take some of your ideas that came out of your own research and institution. See whether on a national scale that, whether these have clinical relevance.

I, as a junior faculty member, got mentorship that I never would have. Because it's on a national scale, not just your own institutional scale. So it's a real opportunity for the investigators too, to fulfill their potential. 

Alicia Morgans: And a nice collaboration between radiation oncologists, urologists, we always need more of both of these types of folks, and then, of course, the medical oncologist as well.

Michael Morris: I think that the group, the committee chairs are all really working together to enhance that sense of collaboration between cooperative groups. So for example, this lutetium trial is a scientific collaboration with NRG, the Radiation Oncology Cooperative group. And Felix Feng who is the committee chair there. He and I work very closely. We try and have all our junior people working together across groups and across disciplines. And from a professional development standpoint, that's great. From a scientific standpoint, you get the expertise of both groups. And from a patient access standpoint, you get access through the radiation community and through the medical oncology community. 

Alicia Morgans: Absolutely. So what are the next steps ... one of the things we always talk about is the influence of these imaging technologies that are coming in. How are these things affecting where the GU committee is going next?

Michael Morris: I think that's even a broader question than the GU committee. It's really a question for where do we as a prostate cancer research community go with this. In the United States, we do have, at least, FDA approval around choline and fluciclovine. What we don't have is approval for PSMA based imaging. Which is really widely available in other countries. Our patients really do want these imaging studies, because they reveal disease much earlier than standard imaging. And plus, it really is direct tumor imaging rather than indirect imaging through bone scans. And it's quantitative, and it allows you a better view of the distribution of disease. So we are being influenced in terms of both our practice and our trials. By having this information, because patients are coming in with that information. 

What we don't have is the insight into how to use that information. And I think that now, both in terms of industry-sponsored studies and cooperative group studies, we need to be aware that patients are getting these scans, that there can be decision making and bias around them. And instead of just observing those phenomena, we should be building those into our trials. So that we can co-validate whatever the endpoint is, in the therapeutic component of the trial, as well as the imaging endpoints to look at prognostication for the pretreatment scans and response indication in the on-treatment scans. Doing that is really difficult. Because there isn't universal reimbursement around these. So we're struggling in the U.S. with the availability and approval issues of getting these scans done and then in actual deploying them, how do we get the patients reimbursed for them?

So these are real challenges that we face. We also face the challenges when the patients just come into the clinic with these scans of what to do with that information. And I think, my sense is that there's a lot of off-protocol guessing. Instead of on protocol investigation. I think that's particularly true where these scans are more ubiquitously available. There's a lot of SBRT being administered to patients who have isolated lesions that are identified. There's a lot of surgical modification for patients who are going to prostatectomies or salvage lymph node dissections, based on this information.

There's probably the application of systemic therapy when you see early disseminated disease that you don't observe on standard scans. And the question is, can we systematize the questions and the answering of those questions in formal clinical trials? And try and reduce the amount of anecdotal data generation and guesswork that we're all doing in order to really get the answers for how to use these.

Alicia Morgans: Well if anyone can do it, and maybe that's a process of co-validation like you mentioned, I think the cooperative group system is one group that can do it. And something for us to strive for as we continue to move forward.

Michael Morris: Absolutely.

Alicia Morgans: So I sincerely appreciate your time and your expertise and perspectives.

Michael Morris: Oh, it's my pleasure.

Alicia Morgans: Thank you.

Michael Morris: Thank you, Alicia. Thank you for interviewing me and having me here.

Alicia Morgans: Great.
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