Dr. Maha Hussain Video (Text Version)
The Prostate Cancer Clinical Trials Consortium (PCCTC)
Dr. Howard Soule
I’d like to introduce Dr. Maha Hussain from the University of Michigan, who is a Professor in the Department of Internal Medicine and Urology. She’s also a member of the Prostate Cancer Integration Panel and the principal investigator of the study site at the University of Michigan at Ann Arbor. Maha is steeped in—in skills and regulatory science and works very closely with basic and translational scientists at the University of Michigan. And we had the privilege this morning to hear Arul Chinnaiyan speak; it’s Maha’s responsibility to make sure that—that Chinnaiyan science sees its way into the clinic and she’s doing that in a very productive and meaningful way. So Dr. Hussain it’s a pleasure to introduce you.
Maha Hussain, M.D., FACP; Professor, Department of Internal Medicine and Urology, University of Michigan
Thank you very much. It certainly is a pleasure to be here and I will tell you it’s an absolute honor to not just to work with a group of very smart and dedicated physicians and scientists but actually to see the advocacy of the patients and their engagement in this. And I think they deserve a round of applause because without them to be honest with you—without them and their advocacy we will not be here.
My task today is to give you a flavor of who we are, and I must wear my glasses so I could see. I wanted to begin just to set the stage as a clinical researcher and clinician—what is important from my end. And when I see a patient I want to see a cure written all over his chart and not just we’re going to just gradually prolong your life and make you feel better. So ultimately we shoot for a cure, but to get to a cure there are multiple milestones we have to go through, and certainly prostate cancer for those of you who are not familiar with the—the picture on the right, this is basically what an end-stage prostate cancer patient skeleton would look like.
The patient—it’s a deadly disease; it’s—prostate cancer lagged behind many solid tumors for many decades, and in fact up until the year 2000 there was one drug that—actually there were two drugs—one was not used and the other one was Mitranzantrone that was FDA approved. Luckily as focus increased on the disease and understanding its biology more drugs made it into the FDA and got approved and you see a list here of three drugs that were approved based on survival prolongation and that is just since 2004, following different mechanisms of actions. Abiraterone is before the FDA for the summer. We anticipate hopefully that it will also be approved. Different other agents were approved for different purposes. But all of these treatments as good as they are, they are marginal in their efficacy at best in that they’re not curative and they prolong life, not by long.
Sadly though as much as there has been positive trials, I point out to that you that in the last 6 years there have been nine negative Phase 3 international or mostly U.S. trials. Imagine the pressure on the—on the patients, the patient resources, the human resources, intellectual resources, and dollars that went into these efforts. Now to complicate matters further, there are multiple challenges as science expands that are more challenges to the way we actually look at drugs and develop them. And so we’re having to shift as we understand more about the biology of prostate cancer to look, as you hear this morning, about the different gene fusions. For example, I could see where we begin to look in the future at—not that as an adenocarcinoma but what molecular feature does this cancer have. So we’re moving from morphology to molecular profile but then when you’re talking about molecular profile, just because something is expressed in a tissue does not make it an important target or biologically relevant at a patient level, forget about the preclinical aspect of things.
Once we take the things to the clinic not everything we find preclinically translates and that’s why it’s very critical to have a seamless transition and an efficient discovery and—and implementation-type processes. And of course, what we want to do is maximize the benefit for those patients who are likely to benefit from something and minimize exposure to toxic treatments, but by default that means we’re going to look at smaller and smaller patients which means collaboration becomes very important so that we can find these patients and offer them the novel treatments that we have. And clearly, and this may be technical, but certainly alternative clinical trial designs and statistical designs and so on are very critical.
So this is where we come in; we’re sort of like this—the—what’s the—the ghostbusters so to speak. This is the PCCTC and it really is a—it’s an honor for me to represent the group. It’s a group of 13 institutions, academic institutions. The PIs are listed here; for sake of time I will not go through that. Every one of these PIs and their teams in their institutions have a tremendous expertise specifically in the area of prostate cancer. Our mission is to design and execute scientifically based early clinical trials. That’s Phase 1 and Phase 2 clinical trials, either single agents, combinations, and what we hope to do is prolong life for patients, ultimately cure this cancer. So this is our history.
Howard described to you how things started. This was officially started as the PCCTC in 2005 following funding from the Department of Defense and the Prostate Cancer Foundation and their collaborative successful initiative. We were awarded—the first dollars came in January of 2006; at the time we were eight centers. In 2007, two additional centers were added and luckily none of the previous centers lost their funding. And then in 2009 we became 13 centers and essentially the—everybody who was around—continued around again, a testament to the fact that somehow we were doing things right and that under a peer review mechanism, people felt that there was enough deliverables from the different sites.
There are milestones; this is not a club. This—there is absolutely hard core milestones in terms of science being introduced, clinical trials being introduced, numbers of patients accrued and so on. We are equal partners in the process and the award is—is scheduled to end in 2014. If God willing there is more money, we would love to compete again and if not we are actually working very hard through the leadership of the coordinating center to create a self-sufficient operation so that we can carry the good work that has been started. The group is helped by a coordinating center led by Dr. Scher, Howard Scher, and Mike Morris. They have a fantastic team working for them with increasing capacities as far as statistical, regulatory, contracting, and so on, and for the sake of time I’m not going to be able to go through all of those details.
So I want to share with you some of our activities for the last 5 years. One thing I would say, just because we work well together and we’re colleagues, we’re not shy to tell each other that this concept is no good and we will not adopt it. And so we want to make sure that you understand that this is absolutely peer-reviewed internally. And even though there is 133 concepts, there was somewhere about 20% of the concepts that did not get adopted; several of them went into activation, several are now active trials, and we’ve completed 48 trials and several have been already reported. And I would encourage you in the poster session to actually go and check out some of the presentations from the different team members.
Most importantly and this is the partnership with patients, more than 2,500 men participated in these particular trials. And was mentioned, eight agents, and I apologize if this doesn’t show very clearly—at least you’ll hear about two of these agents, Abiraterone and Ipilimumab will be discussed, but several other drugs such as the statin Ipsutin and so on made it into Phase 3 trials. And that’s the whole point is to expedite the early discovery phase, decide on a go—no-go; is this drug worth it or not? Let’s move it if it is worth it into Phase 3 trials.
Now this is just the list and I put it in—I couldn’t resist as a clinical researcher to talk about a little bit of science. So this is going to be more of a showing you the different drugs that we have looked at in the past, some of the drugs we’re working on, and the different mechanisms of actions down there. And I specifically put that for you to point out several things. From those of us sitting on the clinical end, we’re not wedded to a particular pathway or target; we look at the totality of the data and when we see there are—that the magnitude is such that it’s worth investing into a clinical trial, we proceed with it and that’s a collective decision that’s made by the group. So you can see that it’s a lot of drugs belonging to different sources—pharmaceuticals, NCIs, and so on and some of them are actually homegrown-based science.
The other thing I want point out and again this is—perhaps it doesn’t show very well but on the far end here what you will see is the different stages of prostate cancer starting from early-stage disease all the way to the terminal phase of the disease in its different formats. And what you will see that—our portfolio is quite full; we tried to stagger things to make sure the pipeline is always full with something for these patients, available at different sites. These are just an example of the letters of intents. These are concepts that have been proposed and are—are accepted in the work of being developed into clinical trials. These are intermediate-stage clinical trials. And these are trials in the green that have—that are nearing their final accrual. And this is really just to give you again a flavor.
So what are our key accomplishments in the last 5 years? I think the most important one of them is we did what we said we would do—that we’re going to serve patients by providing them access to clinical trials and over 2,500 men were enrolled in these trials. In fact, some statistics that the coordinating center helped me get that our clinical trials represented by 26% of industry-sponsored trials and more than 10% —about—more than 13% actually of NIH-funded trials. Over 10% of the Prostate Cancer Foundation—I’m sorry—PCCTC patients are from this proportionately affected population. We have partnered with pharma because we do believe that ultimately everything is a partnership to try to bring in agents within our priorities to the patients. We have harmonized the processes and have major efforts with regard to biomarkers trying to tag with the SPORE grants, funded institutions. And of course, as I said, more importantly eight agents now have been furthered into three trials.
Now this picture of a very handsome group of people is actually our team. And I want to say that research is what cures cancer and what makes a difference. And our overarching objective, because I took orders from Howard and I will say yes, sir—is impact and change the standard of care. And the only way you do that is with really translating science into the clinic. You can also find us at www.pcctc.org. Thank you.