Dr. Matthew Roe is a Professor of Medicine at Duke University’s Clinical Research Institute (DCRI), the Faculty Director of the Global Outcomes Commercial MegaTrials program, and the Director of their Fellowship Program. (The DCRI’s databank is the world’s oldest and largest cardiovascular database.) He has participated in the leadership and conduct of numerous clinical trials focused on therapies for acute coronary syndromes and chronic cardiovascular disease. He is keenly interested in clinical trials’ operational conduct as well as in national and global academic collaborations.
Prostatepedia spoke with him recently about a clinical trial he’s leading that looks at the cardiovascular safety of Firmagon (degarelix) versus Lupron (leuprolide) in men with prostate cancer.
What’s the thinking behind your clinical trial comparing cardiovascular safety of Firmagon (degarelix) versus Lupron (leuprolide) in patients?
Dr. Roe: Years ago, a number of studies were done that showed a potential signal for increased cardiovascular event risk among patients with known cardiovascular disease who were receiving androgen deprivation therapy, the standard of which is Lupron (leuprolide). Eventually, there was a document released by professional societies, including cardiology professional societies and urology professional societies and a black-box warning on the label of that drug, that there is the potential that patients with known cardiovascular disease who receive this therapy could have an increase in cardiovascular risk. That therapy is used to treat advanced prostate cancer and has known benefits there. These professional societies were trying to set up a shared decision-making model with prostate cancer patients and their physicians to better understand if this therapy should be used, and if so, how should they monitor it.
Then Firmagon (degarelix) was developed as a different type of androgen deprivation therapy with a different target, having similar efficacy in treating prostate cancer. Some post-hoc analyses suggested that patients who receive Firmagon (degarelix) might have a lower risk of cardiovascular events when they have known prior cardiovascular disease while receiving this drug as treatment for prostate cancer.
All these studies that were done were retrospective studies that weren’t meant to answer that question.
The trial we’re conducting, the PRONOUNCE Study, was designed as a prospective rigorous randomized trial to compare those two treatments among patients with prostate cancer, to understand if there is a lower cardiovascular risk with Firmagon (degarelix) versus Lupron (leuprolide).
What can a patient expect to happen during the trial?
Dr. Roe: A number of sites in the United States and other countries are participating. In those sites, urologists or oncologists who treat patients with prostate cancer are evaluating their patient population whom they’re considering treating with androgen deprivation therapy.
If they meet their eligibility criteria for the trial, they discuss the trial with them. If the patient is eligible and he chooses to participate, then he is randomly allocated to receive Firmagon (degarelix) or Lupron (leuprolide) for 12 months. The therapy is provided to him as a study participant. He will be seen every month during the study to do a check in and assess whether or not he has experienced a cardiovascular event and to optimize his background treatment therapy for both prostate cancer and cardiovascular disease.
I work at the Duke Clinical Research Institute. We’re the academic coordinating center, working with the sponsor Ferring Pharmaceuticals to help design, run, and conduct the study. This is a collaboration between academic experts and the sponsor. We have a steering committee of academic experts—cardiologists like myself, urologists, and prostate cancer oncologists to work together to conduct this study.
Are there any specific eligibility criteria that you’d like to call attention to?
Dr. Roe: Yes. We are looking for patients with prostate cancer who meet the criteria to receive androgen deprivation therapy. I’m not going to go into the exact details, but the trial is for those eligible for advanced prostate cancer treatment. These would be people who would not be receiving a prostatectomy or radiotherapy treatment. These patients have to have a known history of prior cardiovascular disease, which we confirm. We work with the study sites to implement that confirmation, because urologists and oncologists treating patients with prostate cancer aren’t really experts in cardiovascular disease.
We work with them to ensure that they’re meeting those criteria and that they’re treating patients appropriately. In many cases, a cardiologist will work with the site investigator, who is an urologist or an oncologist, to help conduct the study.
I’m sure there are quite a few men with advanced prostate cancer who also have cardiovascular disease.
Dr. Roe: Yes. It’s estimated that about 35-40 percent of men with advanced prostate cancer will have a known history of cardiovascular disease, partly because both conditions are common in older age. That is one of the strongest risk factors for both prostate cancer and heart disease, so we see the convergence of those two conditions.
If someone reading this is interested, who should he contact?
Dr. Roe: We do have at least 30 or so sites in the United States. If someone is interested, he can contact me directly and then I can put him in touch with the right people. One of the challenges is that only a certain number of physicians who treat patients with prostate cancer would be interested in participating and being investigators for the trial, so matching them with patients around the country is always a challenge. We are happy to help patients who are interested in participating have that opportunity, even if their local doctor may not be the one who’s the investigator.
Is there any fee for patients to participate?
Dr. Roe: No. They receive reimbursement for their travel to come to and from the clinic for their visits. They receive the therapy that they’re getting, Firmagon (degarelix) or Lupron (leuprolide), for free. There are no costs for the patient; they just have to volunteer their time. We recognize that and we share information with the patient.
At end of the day, we will share the information from the study directly with the study participants, to help them understand their contribution and what it means going forward. We overtly honor the volunteerism and altruism of the patients.
Is there anything else you’d like patients to know, either about this trial in particular or the context in which it occurs?
Dr. Roe: If a patient who has advanced prostate cancer and known cardiovascular disease is being considered for androgen deprivation therapy, it is important that he speak with his cardiologist. (Presumably, both a cardiologist or cardiovascular specialist and an urologist or oncologist would treat him.) He needs to ensure that all the providers have a discussion about what the best and safest treatment would be before therapy begins. Obviously, this trial is not completed yet so we don’t have any answers. In the meantime, it is certainly in the patient’s best interest to ensure that his providers are communicating and trying to jointly determine the right approach.