Mr. Jake Vinson is the CEO of the Prostate Cancer Clinical Trials Consortium (PCCTC), a multicenter clinical research organization that specializes in trailblazing prostate cancer research.
Prostatepedia spoke with him about clinical trials for prostate cancer and the pioneering work of PCCTC.
How did you get involved with clinical research administration and patient advocacy?
Mr. Jake Vinson: My involvement in clinical research dates back to college years. My part-time job was working in a clinical research organization, and I really enjoyed that environment and the work that was a being done. I progressed through college and graduate school and subsequently was able to run a number of clinical research organizations. That process brought me to New York about ten years ago to be involved in the Prostate Cancer Clinical Trials Consortium.
As far as patient advocacy, I’ve grown to distinguish two threads of advocacy, one being patient advocacy and the other being research advocacy. My path in working through drug development and clinical trials has really been geared more toward research advocacy than patient advocacy.
Patient advocacy considers needs at the individual patient level —ensuring they’re getting to the right appointments and having the right tests and seeing the right experts. Research advocacy makes certain research is funded appropriately. It ensures that research is being watched over in the right way and that it intersects with the patient advocate component. It’s an interesting distinction, but one that I think is important.
What has kept you engaged over the years?
Mr. Vinson: I’ve always found the organizations that I’ve worked with and have run sit in a very interesting and unique spot in the continuum of cancer research in that they connect academic investigators who are the subject matter experts; they think about new ways to develop drugs and treat patients; and they connect them with the pharmaceutical and biotech companies who are developing drugs aligned with the scientific programs of investigators. And finally, there is the part that we talked about—the advocacy component. Making sure that patients at the clinical sites where they’re being cared for have access to these research studies.
What’s kept me involved is being in the middle of that triangle. Not necessarily working in a hospital or in an academic research center. Not necessarily working in a pharmaceutical company. And not necessarily working at a clinic site or a doctor’s office, but really creating an infrastructure that connects all of those things. That to me has been exciting.
What is the Prostate Cancer Clinical Trials Consortium?
Mr. Vinson: The Prostate Cancer Clinical Trials Consortium (PCCTC) is an organization that has been around for going on 20 years now. It was originally created by the Prostate Cancer Foundation (PCF), which is the world’s most significant philanthropic prostate cancer research-focused organization. They recognized that there were obstacles in the collaboration of what were considered the top prostate cancer academic programs around the United States. They worked to put some funding in each of those centers with the sole goal to eliminate barriers to working together on clinical trials. This was some time ago.
That idea was subsequently leveraged into an initiative through the Department of Defense [DoD], which here in the United States has the Congressionally Directed Medical Research Program. Within that program is the DoD Prostate Cancer Research Program (PCRP).
Fifteen or so years ago, the PCRP put in place an offering for a Clinical Consortium Award. This was a formalizing effort to PCF’s idea. Memorial Sloan Kettering Cancer Center (MSK) applied for and became the coordinating center for this Consortium Award. Eight other centers were selected as participating sites. This created the coordinating center site model, or a consortium, to bring together and understand what clinical trials everyone was working on, where the intersects were, and where the collaborations across sites could happen efficiently and effectively. The aim was to shape and understand the landscape of prostate cancer drug development to take out those preconceived notions of competition and show areas where cooperation could happen.
MSK still holds that Clinical Consortium Award. We’ve had a number of sites come in and out over the last fifteen years.
A number of years ago we identified that to really be effective and to scale our infrastructure to support all kinds of prostate cancer research we needed to have a better business-operating model than something based solely on a grant from the from the DoD.
So, just over five years ago we spun off a business, which is now the operating company for the PCCTC. That business exists to conduct multicenter clinical trials so that all of our participating sites around the world now can work together on selected clinical trials. We let the investigators do what they do best, which is develop the ideas and ways to study the drugs. We let the clinical research sites and the clinics do what they do best, which is treat their patients and manage them on a study. This in turn lets us handle the regulatory, data, and biospecimen management—all of the things that go on behind the scenes of a clinical trial that investigators and sites aren’t specifically suited to address. Through contracts with our pharmaceutical partners we are able to get access to their drugs that are developed by the pharmaceutical companies and then put those into the clinical trials that our investigators are developing. That is how our model works.
That’s a unique model, isn’t it?
Mr. Vinson: It is fairly unique. It has attributes from a number of different businesses in this space. It in and of itself functions in a fairly unique way.
What kinds of clinical trials do you run?
Mr. Vinson: The organization was originally established as an early phase drug development group, so our intention is to identify new drugs, new classes of drugs, or new targeted drugs to treat prostate cancer patients of all stages. We do very early studies with patients who are newly diagnosed or often times we do studies with very late stage patients who maybe have seen a number of lines of treatment already.
We really look at the continuum of disease states from very early diagnosis to very advanced disease. We identify which studies would be most reasonable to put in place in all of those spaces so that we’re not necessarily constantly overlapping. We want to have studies distributed fairly evenly so that patients of all different disease states or manifestations within states would have an opportunity to be in a clinical trial if treated at one of our sites.
We have traditionally focused in Phase I and Phase II development. Because we’ve been fairly successful in that, we have now opened our first Phase III study, which is a much larger trial. A Phase I or a Phase II trial has from 30 to 100 patients. A Phase III study can have as many as 800 to 1000 patients.
I’ve heard that it’s difficult to enroll patients in trials and that frequently trials don’t get the number of patients they were originally seeking. Why do you think this is?
Mr. Vinson: There is data that shows this is absolutely true. What we know is that, in the United States, 3 to 5 percent of cancer patients go on to clinical trials, which is obviously not very many. Even within the number of eligible patients, only 25 percent actually do enroll in a clinical study.
I should also add that because of the way the science has taken us, we are now looking to enroll patients with specific molecular characteristics. These molecular characteristics are biomarkers, or gene signatures that we see in tumor tissues or blood, which can often be found only in a very small percentage of patients. A particular marker that we think a drug works in may only appear in 10 or 15 percent of patients. A fairly small group of patients go onto studies to begin with; molecular inclusion criteria makes this number smaller.
This is creating a conundrum whereby we have to cast a much wider net, meaning we have to have more sites collaborating to identify patients eligible for enrollment based on their unique molecular characteristics. These are interesting challenges. The science to be able to do this is incredibly significant and will be impactful to patients, but filling those clinical trials is difficult. We would think we would want to include more patients in studies, but because we’ll be able to parse the patients into much smaller groups with specific molecular characteristics, it is becoming more challenging.
You need to cast an even wider net to find these patients?
Mr. Vinson: That’s exactly right. We originally worked with eight centers. We now have 14 centers that are formally part of our group with another 50 sites in the United States who are affiliate participants. Those centers have gone through our qualification process; we know they have quality research programs at their clinical sites and have the opportunity to open studies that we’re developing as well. That is one of our strategies, to circumvent that conundrum of great science that then doesn’t enroll the patients we planned.
There are some regulatory implications here: there has to be great caution in doing clinical research. We would offer that, when you’re using drugs in a very early development space, meaning this is often the first time that the drug has been used in patients, you want to make sure that the patients are appropriate to be treated with those drugs. What you can’t do is just flood your study with patients because you might miss a safety signal, or you might miss a dosing change. There are too many variables happening at the same time. We know that is part of the issue.
From the other end, it’s a lot of work for the clinical sites to participate in the studies. We do our best to fund our sites appropriately, but there are so many pressures on our clinicians in terms of how they’re managing their electronic medical records and how many patients are expected to be seen by their clinics and their sites. Their additional bandwidth to enroll patients under clinical trials is finite. You have to consider all of the safety and regulatory requirements for the studies themselves and the external factors for the investigators working on the studies.
Finally, we and others have been working for a long time on research and patient advocacy.
When a patient comes in and they’re approached about a clinical trial, we don’t want that to be the first time they’ve ever heard about clinical research. That’s an entire other discussion that requires a full education to make folks comfortable with clinical trials. Those are the three angles that we try to work on in alleviating those barriers.
Why should patients consider joining a trial? What are some of the benefits?
Mr. Vinson: Depending on the study, the potential for benefit can vary. There are potential advantages to getting access to a new drug, which could in theory have great benefit to them, but again, this is called research. We don’t know exactly what the outcome will be, but there is the opportunity to get access to more cutting-edge treatment that could have an upside.
The other lens to think about is that research is advancing the field for the men who will follow. If we didn’t have the clinical trials that we did 25 years ago, we wouldn’t have the drugs that are now proven to extend life . There were men who joined clinical trials to get those drugs approved and tested as safe and efficacious or that worked in controlling cancer. We would offer that there’s great opportunity to, in a safe way, contribute to the advancement of treatments for future generations of men. We think that’s important.
Is there a certain time point when a man should start looking for clinical trials?
Mr. Vinson: Ideally patients should learn about the clinical research process at the point of diagnosis so they understand the advantages and risks of trial participation. Men should feel comfortable asking their healthcare providers about clinical research opportunities at any point in their care.
From a drug development perspective we traditionally evaluate therapies earlier in the disease continuum only after establishing efficacy in more advanced disease. We think there is potential for a cure in very early disease and are now designing trials of drugs that gave benefit in very advanced disease in this space. We really feel like there needs to be clinical research participation from very early on while we continue to look to control disease that has spread and become more advanced. In short, there are opportunities to participate in clinical trials starting at all points of care.
I suppose if you start a conversation early on with your doctor, even if there’s nothing appropriate for you at that time, if something does come up, she is more likely to bring it to your attention.
Mr. Vinson: Absolutely. Opportunities are continually turning over: new studies are opening and prior studies are closing. We know patients from all over the country who have been on multiple clinical trials. Many do very well. We think it’s exciting that they’re open to that.
Do you have any suggestions that you think patients should keep in mind as they evaluate trials?
Mr. Vinson: There are so many different types of studies out there. I think a Phase I study may have requirements in it for some additional testing or additional visits because the endpoints of that kind of study are to evaluate at very specific timepoints how a drug is being received and metabolized or processed by a patient.
The bigger and later stage Phase II or Phase III studies are designed to be as continuous with standard of care as possible so that it is not a burden or inconvenience to the patient. All of those things have to be taken into consideration. An honest discussion with your healthcare provider, healthcare team, and the research coordinator or research nurses, is really the best way to figure out which situation is going to be best.
How the results of your trials are reported? Are all trials reported? Are patients who participate in trials informed of the results?
Mr. Vinson: We publish and present all the results from our research studies. We ensure that we have the right to do that with our partners —our research sites and our pharmaceutical and biotechnology partners as well as the groups that own the drugs that we work on. We have contracts with them that are very clear in that we have the ability to put the data together, to put the outcomes together, and present them to the public. That’s done through a number of different methods— meetings where abstracts are presented to manuscripts submitted to professional journals.
Your point is a good one about returning results to patients. Many sites have programs to distribute the outcomes to those patients. This is done at the site level. The challenge for us is that we don’t get, in almost all cases, direct contact information for patients. When a patient goes on a trial, the local treating clinicians certainly know that patient well. But we give that patient what we call a subject identifier. This is a random number that is created so that we can then track that patient without having any personal information about the patient directly. We have their health outcomes data, but we certainly don’t know where they live, or what their phone number is, or how to email them. Returning those results directly to a patient from the entire study as you can imagine, is something that would be challenging.
Informed consent forms reflect the growing number of molecular testing and sequencing performed in trials. Before patients participate on a trial they are clearly notified on of which test results would be returned to them personally. This can vary from study to study.
But to your point, we think it’s important when we’re doing research tests that could have implications for a patient or their families, especially when we’re talking about genetic testing, that we have a mechanism to inform them if there are findings that need to be followed up. As you can imagine, there are implications for family members as well in genetic research. That happens through the informed consent process, and again, at the site level where the patient’s being treated.
I guess if you’re going to make a call for men to join trials for altruism’s sake and for the furtherment of science, they might want to know if the research actually did advance our understanding of prostate cancer.
Mr. Vinson: There are sites that do that: when outcomes are published, they distribute them to patients who are interested. In addition, publications can be searched for independently or requested from the clinical investigator.
It takes a long time for some of these studies, though. If you’re the first man to go into a particular study and it’s going to be a 100-patient trial that takes over a year, you’re already taking about 18 months to enroll that study. Then we do all the follow up, which could be another two years. Then we do all of the data analysis, which could be another six months. It could be three to five years from the original patient enrolled to publication. It can certainly be a long process.
Are any particular PCCTC trials looking for patients that you’d like to highlight for my readers?
Mr. Vinson: We’re doing a study called IRONMAN. IRONMAN is an international registry for men with advanced prostate cancer. We’re working with eleven countries around the world in collaboration with the Movember Foundation. (Movember is the Australian-based organization that grows mustaches and raises money every November for men’s health and awareness.) One of their core programs is a prostate cancer program, and one of their key projects is the IRONMAN project.
The PCCTC is the global coordinating center for IRONMAN. The study does not have a specific drug treatment requirement and instead tracks patients receiving standard of care therapy. Participants will be recruited across academic and community practices from around the world to facilitate a better understanding of variations in prostate cancer treatment. Patients who enroll are followed prospectively over several years. We collect data on what treatments their physicians have given them as well as some high-level clinical outcomes data from those treatments and track how treatments are sequenced or given in combination around the world.
The second part of the trial examines patient reported outcomes. We have particular surveys that study participants complete every three months that examine their quality of life and how they’re feeling across a number of domains. Then thirdly, we have a biology component, in which we collect blood samples when patients join the study and then again each time they change their treatment. This helps us understand, to the point I was making earlier, what changes are happening at the molecular level and what’s changing in the biology of the patient. Then finally, we’re asking their physicians to answer a brief survey telling us why they recommended changes in treatment, which will give us insight into the variations in prostate cancer treatment across different centers and countries. By collecting blood samples, patient reported outcomes, clinical data, and physician surveys, we can tie together the biology of the patient’s disease with the patient’s reported experience on a given treatment with the clinical data on their response to treatment. Putting all of those things together with 5,000 men around the world in eleven countries is going to give us an incredibly rich dataset to be able to mine and understand what treatment patterns may be best for particular patients. What’s unique about IRONMAN is that we are not just collecting information on how patients do clinically, but also how the patients themselves report they do. Through IRONMAN, we will also understand the biology of those patients and how it changes over time, and we will be able to tie those outcomes to the clinical outcomes to develop tests that can potentially let us predict how patients will do on a specific treatment.
IRONMAN is an exciting study. Centers around the world are now open and actively participating in the study. We have nearly 700 patients accrued from 7 countries, with 4 more coming on board soon. It’s an exciting project, and something that is very different than a standard Phase I or Phase II clinical trial, but it’s certainly something that we think is going to result in an incredibly powerful dataset for investigators to use into the future.