Clinical trials are the basis of modern medicine. Through a series of phases, clinical trials strive to find more effective treatments with fewer side effects. For men with limited options, clinical trials can be a great way to access the newest treatments; however, choosing the right clinical trial can be difficult. This episode discusses pros and cons of participation, how patients can benefit, and addresses some common concerns and misconceptions.
Dr. Scholz: [00:03] We’re guiding you to treatment success and avoiding prostate cancer pitfalls. I’m your host, Dr. Mark Scholz.
Liz: [00:09] And I’m your cohost, Liz Graves.
Dr. Scholz: [00:13] Welcome to the PROSTATE PROS podcast.
Liz: [00:17] Clinical trials are the root basis for modern medicine and they’re vital for the development of new treatments. This episode, we’re going to talk about pros and cons of clinical trials, who can benefit, which clinical trials to be most excited about. We’ll also address some concerns patients might have about participating.
Dr. Scholz: [00:37] Yeah, I mean, clinical trials are how doctors decide what to do for patients. But today we’re going to talk more about how patients can extract a benefit from participating in a clinical trial. Some medicines are only available on clinical trials, they’re not FDA approved yet and trying to make a determination if you, specifically, would benefit by being in a clinical trial, getting an investigational drug is what this podcast today is about.
Liz: [01:05] So which type of patients in prostate cancer are looking for clinical trials?
Dr. Scholz: [01:11] It’s really important as has been emphasized many times in the past, that there are different types of prostate cancer. We call them stages or five different stages of prostate cancer and clinical trials are usually being performed in people with advanced metastatic prostate cancer, more often the type of cancer that is not responding to traditional medicines.
Liz: [01:34] So these are patients who have limited options left and clinical trials can allow them access to the newest treatments.
Dr. Scholz: [01:42] Exactly. The problem with doing clinical trials is that there are always disadvantages. If there are other FDA approved medications that have been already shown to prolong life why wouldn’t patients use those first, especially since they are typically covered by most types of insurance?
Liz: [02:05] I think one concern people have is that clinical trials are either not covered by insurance or they’re expensive. Is this true?
Dr. Scholz: [02:12] Actually no, most of the time, clinical trials will provide the medications free of charge. I think the disadvantages of clinical trials are that they’re somewhat cumbersome, there’s a lot of paperwork, and it’s very formalized. So people are treated in a very uniform fashion, there’s less room for creativity and adjustment of doses and things like that. There’s a major inconvenience to clinical trials. Then of course the way that the medicine is used or whether or not there is a potential for getting placebos, these things can also be a disadvantage for patients who are participating in clinical trials.
Liz: [02:50] I think one other thing I was looking at clinicaltrials.gov to find the list of what’s happening in prostate cancer. A lot of the eligibility criteria is really strict, so I think that can be kind of a limiting factor as well.
Dr. Scholz: [03:05] Yeah, that’s a very good point. If people don’t meet the criteria, then they can’t enter into the trial. I think it’s challenging for patients to parse out, do they have the eligibility criteria that will qualify them? It’s not easy to read these trials and it’s not like you can learn a trial and now you understand trials, every trial has its own unique design. So the patients that are going to be able to utilize the vast industrial, investigational complex are those that can get online, read trials, and understand the eligibility criteria to determine if they would fit into that trial. So it’s a shame to waste a lot of time, understanding the pros and cons of a trial only later to learn that you don’t qualify. Maybe you’ve had one too many rounds of chemotherapy or some other factor that kicks you out. The typical problem is that these trials are not flexible. Because you’re a nice guy they’re not going to give you a card to get into the trial. You must fit the criteria.
Liz: [04:10] So clinical trials are another reason that you should be knowledgeable about your health and maybe have copies of your medical records. You can reference those to see if you can fit into a trial. How do patients decide if this is even something they want to pursue?
Dr. Scholz: [04:26] Well, as you mentioned previously, Elizabeth, the patients that have good options and there’s thankfully a number of good options for men with advanced prostate cancer now probably should go with those first. But it’s always good to have a backup plan. Many treatments will not work indefinitely and when things are going well, it’s good to be looking into what you would do if the treatment you’re using right now stops working. Your doctor may have a clear plan and it may make perfect sense with drugs that are already FDA approved, if he hems and haws and says, “I don’t know exactly what the next step would be,” perhaps now it’s time to start looking into whether you would be eligible for some of the different clinical trials that are out there.
Liz: [05:12] So we’re talking about men who have limited options. On an earlier episode, we talked about off-label therapy and some of these clinical trial drugs can also be used in an off-label way. How do we decide if patients should go the clinical trial route, or if they should get the drug off-label?
Dr. Scholz: [05:32] It may have to do the cost. Sometimes the clinical trial will cover the cost of these expensive medications or maybe convenience. It’s more convenient to simply have your doctor prescribe a medication, which he can legally do using his own judgment. If it’s FDA approved somewhere for another cancer, perhaps. This brings up the whole subject, which we’ve covered in the past of genetic testing as a way to determine if an off-label medication might fit for a patient, who’s got limited options otherwise.
Liz: [06:08] So whether someone’s using the drug in an off-label way, or they’re on a clinical trial will you be checking their PSAs and just making sure their side effects are kept in check?
Dr. Scholz: [06:20] Precisely. The issue is with any treatment for men with advanced prostate cancers is we really want results. The type of people that are going into clinical trials have often tried a few different things and they’ve stopped working. So we don’t have time to dilly dally around. We need results. That usually means a decline in PSA once the treatment has started, or if people are having some bone pain that the bone pain goes away, some clear evidence for benefit. This seems kind of obvious, but it surprises me sometimes that patients will patiently wait on a medicine, even though the PSA is steadily rising month after month, when really it’s time to move on, if after two or three months there isn’t evidence for a response.
Liz: [07:00] That’s actually something I learned while researching this is that patients can stop clinical trials at any time, if they’re not responding, or if they’re having bad side effects, you’re not locked in to the clinical trial.
Dr. Scholz: [07:13] Yeah. Excellent point, because even though this is research, ultimately ethics demands that patients be treated in a fashion that’s going to benefit them and not leave them worse off than they started before.
Liz: [07:27] So there are different phases of clinical trials and each has kind of a different set of requirements. Can we start talking about phase I trials?
Dr. Scholz: [07:36] Yeah. So phase I, II, III, and sometimes even phase IV. Phase I is a brand new medication, so new, no one knows what the proper dosage is. The only way to learn is by giving steadily increasing, incremental amounts to different patients to see, at what point did they start developing side effects? So patients that are participating in phase I trials typically are, I would guess more desperate because there’s no proof yet that it’s going to work in humans. There’s probably been studies in animals, or other factors that indicate possible benefit, but phase I trials are dose finding trials. If you are planning on going into a phase I trial, you really want to ask the investigator, have they tested it in other people yet? Are there any signs that it’s causing benefit and have they started to see any side effects? For safety reasons they usually have to start at a very low dose, or if you’re the first patient to go onto a phase I trial, there’s a good chance that the dosage will be too small to benefit you.
Liz: [08:41] After a phase I trial is completed and successful. Then next comes phase II.
Dr. Scholz: [08:48] Phase II trials are for patients who are going to be getting a drug that in a phase I trial was shown to be somewhat effective and also not excessively toxic. So the advantages of a phase II trial are that people will be getting the proper dosage of the medicine. It’ll be with a medicine that we think has activity. Another good thing is that everybody gets the medicine. As we move on to talk about phase III trials, we get into the whole issue of placebos.
Liz: [09:18] Okay. So phase III trials grow a little bit larger and you’re either comparing the new drug to the standard treatment, or they’re randomized with placebos, as you just said.
Dr. Scholz: [09:29] So phase III trials are usually pretty exciting because the phase II trials showed a benefit and phase III is necessary for the FDA to approve a drug for legal use in the United States. Therefore the medicine that’s being used is very likely to be helpful. The problem of course, is the risk of getting randomized to a placebo. That is obviously a concern. Sometimes they randomize people two-to-one. So your chances of getting the real drug are two-thirds. The chances for getting the placebo is one-third also, if you embark upon one of these trials and there’s a known set of side effects with the investigational drug, you can sometimes discern if you are getting the real drug or not, because the placebo patients aren’t getting any side effects whatsoever. If there’s a response, clearly you’re getting the real drug. So patients do have the option of stopping the trial, if when they’re taking the placebo, they feel they’re receiving no benefit.
Liz: [10:31] A lot of the apprehension around clinical trials comes from this idea of getting the placebo. And as Dr. Scholz just mentioned, this likelihood really only increases in the phase III trials. How do you talk about this with your patients? If you have someone coming to you saying “Dr. Scholz, I really want to participate in this phase III trial, but there’s a chance I’m getting the placebo?”
Dr. Scholz: [10:54] Like any other treatment decision we’re looking at risk benefit ratios, we’re looking at what other options do we have? What is the chance at some other second or third line treatment option is going to benefit versus the investigational drug? Sometimes these investigational drugs come into phase III with tremendous optimism. There’s a medication called Lutetium-177 that has just recently completed phase III trials. But in the phase II trials, 30, 40, 50% of patients were responding to this with very few side effects. So there was no doubt that this medication was beneficial. And of course one’s best hope is that you get the medication rather than be randomized to the placebo. But other phase III trials were not so certain that the drugs are effective. Those obviously are less attractive.
Liz: [11:45] All the medications that are used today, like Taxotere, abiraterone have all been through these phases of clinical trials, but there are a number of medications that never made it into the medical world because they failed at these clinical trials.
Dr. Scholz: [12:02] I would say that for every medication, FDA approved that we have in prostate cancer, there’ve been five, ten, or fifteen clinical trials that were just as optimistic and hopeful, but did not show a survival advantage when they were tested thoroughly in phase III trials. We mentioned this because there’s often a false sense that if it’s in a clinical trial, it’s new and improved and it’s going to be better than what’s on the market already. I think that is becoming more common. I think medical research is improving every year and the hit rate on these drug designs is getting to be quite good, but patients need to be careful that just because it’s in a clinical trial, doesn’t mean that it’s going to turn into an effective drug.
Liz: [12:49] So our office does clinical trials. How are you deciding which one of these seem like they will actually help your patients versus which ones you’re just going to pass on?
Dr. Scholz: [13:01] I remember when a drug trial looking at high-dose vitamin D in combination with Taxotere was put on a phase III study and there was so much excitement because all the phase II trials look so good and everyone is already excited about vitamin D, but unfortunately it did not pan out. The high doses of vitamin D with Taxotere gave somewhat lower response rates than the patients who got Taxotere alone.
Liz: [13:31] There are also phase IV trials, which are observational trials, looking to learn more about the drug after it’s already on the market.
Dr. Scholz: [13:40] So the types of questions that pharmaceutical companies ask are in a larger number of patients, once it gets on the market, thousands of people will be undergoing therapy. Are there other rare side effects, for example, that need to be tested for? And the idea is that further experience with how the drug behaves in a larger population could be useful.
Liz: [14:05] If you’d like to see what clinical trials we’re conducting at our office, visit prostateoncology.com. Which current prostate cancer trials are you paying particular attention to?
Dr. Scholz: [14:18] Right now, most of the excitement is around immunotherapy. People have heard about these medications, President Carter had an amazing miraculous response to a medicine called KEYTRUDA, which stimulates the immune system. There are three phase III trials looking at KEYTRUDA in various combinations for men with prostate cancer. There’s also some work being done by Amgen, which tries to garner people’s T-cells to attack cancer directly. They use a bi-specific monoclonal antibody to attract the army cells of the immune system, the T-cells, closer to the tumor to kill off the cancer. Some of the early phase II trials look pretty exciting. The whole field of immunology is so hopeful. We know that we’re only at the beginning and if we can develop this technology and harness it, it’s going to benefit a lot of people.
Liz: [15:15] There are so many clinical trials that it’s often hard for doctors to keep up with them all. So this responsibility falls on the patient’s shoulders. Clinicaltrials.gov is a great place that’s organized, and you can find information there and then bring that information and have a conversation with your doctor.
Dr. Scholz: [15:35] If you understand your stage, you can look at the eligibility criteria and only be looking at the trials that would fit your profile. Also, you know what limitations you have. Can you travel to a different town? Are you willing to go through the hoops that are necessary and the inconveniences to get into a clinical trial? Once you select some potential candidates, your physician can help you decide if it’s really a practical approach.
Liz: [16:04] One last thing to note is we’ve talked about how biased the industry is and unfortunately clinical trials are no different.
Dr. Scholz: [16:13] So the industry of clinical trials is heavily funded by the pharmaceutical companies. I’m extremely grateful for these wonderful new medicines that these companies put in my tool chest to help patients with. But there’s a tremendous urgency to get patients involved in clinical trials. They’re very expensive to run. You as a patient have to be careful that you’re not being hurried into a trial that really doesn’t benefit you. There’s always that potential that any warm body may fit. And if you are a savvy shopper, you can take advantage of these wonderful new drugs. But, if you’re not careful, it is possible for you to end up receiving medications that are very unlikely to help.
Liz: [16:56] As always, it’s important to stay empowered and be proactive about your prostate health. We’ll keep you updated on the subject as more clinical trials emerge. Thank you for listening. Remember to email any questions or topics to email@example.com.