Research studies known as clinical trials have led to countless advances in the diagnosis, treatment and prevention of cancer. These studies test the effectiveness of new medical approaches that can lead to fewer treatment-related side effects and, in some cases, improved outcomes for patients with certain cancers.
But many patients know little about clinical trials, much less what's involved to participate. Listen to City of Hope Radio as Dr. John Zaia, director of City of Hope's General Clinical Research Center, explains how clinical trials work and how patients and their families can make informed decisions about participating in trials.
Selected Podcast
Clinical Trials: Life Saving Research. Might You Be a Candidate?
Featured Speaker:
John Zaia, M.D.
John Zaia, M.D., specializes in Pediatric Infectious Disease, with a particular interest in infections of immunocompromised patients, especially transplant recipients and HIV/AIDS patients. His clinical research involves the development of stem cell approaches for control of HIV/AIDS using gene therapy, and his team was the first to apply such approaches to AIDS lymphoma. His laboratory studies innate immunity to cytomegalovirus (CMV), and he was the principal investigator on the first evaluation in humans of a peptide based CMV vaccine developed at City of Hope. Transcription:
Clinical Trials: Life Saving Research. Might You Be a Candidate?
Melanie Cole (Host): The aggressive pursuit to discover better ways to help patients now—not years from now—places City of Hope among the leaders worldwide in the administration of clinical trials. My guest today is Dr. John Zaia. He is professor and chair in the Department of Neurology and director of the General Clinical Research Center at City of Hope. Welcome to the show, Dr. Zaia. Tell us, what are clinical trials?
Dr. John Zaia (Guest): Clinical trials are a test of whether a new treatment is safe and whether it works. Basically two kinds: There are those that we call therapeutic, that is, the intent of these trials is to see whether the treatment is better, because the outcome is to cure better than the standard therapy. The other is called nontherapeutic, in which you’re just trying to find out a better way to manage a patient, a better diet for the patient, whether exercise programs are better for a patient, whether a diagnostic test is better, that is, you can actually determine whether a person is at a low-risk group or a high-risk group if they come in with a new diagnosis. So, in summary, you have a therapeutic trial and a nontherapeutic trial.
Melanie: When we look at the different types of clinical trials, prevention, or screening and detection, are these all parts of it from prevention of a particular disease all the way through quality of life and in the treatment room?
Dr. Zaia: Yes, they involve the full spectrum. How do you assess a patient on the first day that you see him, that is, how do you determine? Can you categorize him into a person that is going to do really well and therefore does not need aggressive treatment or a patient that is going to need more aggressive treatment? All the way through the process to the end, and then you assess: What that this done to their quality of life?
Melanie: So what would be the benefits to being involved in a clinical trial? What patients would be interested in getting involved?
Dr. Zaia: That's a difficult question, and the reason I say that is that certain of our trials are the first time a new treatment has ever been used in that patient; it’s usually for an illness for which existing treatment just doesn't usually work. When we do that, it's so experimental that it may be what we call a first-in-human trial. We have several first-in-human type of trials here, which means that we don't know what’s going to happen; we're really doing this to see if it's safe. We tell the person that we cannot expect a benefit.
Many of the other trials though are in Phase 2 and Phase 3, we call it. So, once you are out of that first phase, we call it a Phase 2 to see how good a new treatment is, and then Phase 3 is when how good it is compared to the existing alternative. When you get to that part of the trial—and I’m talking, of course, about the therapeutic trials—there is a good chance of benefit. We explain that at least they’ll be getting as good a benefit we think as the standard of care.
Melanie: Dr. Zaia, what does it take for a clinical trial to get the Phase 4, to where it starts to be looked at by the Food and Drug Administration and approved?
Dr. Zaia: Actually, Phase 4 is where it’s approved and then you actually use it in its approved agent. You continue to monitor people that are on that treatment. How do you get to an approved drug is what you are really saying. That is a multimillion-dollar question. I say that because it takes so long for the safety trials to be completed and for the trials to determine, what's the best dose of a new treatment? Then the large population studies is when you are actually comparing this to standard of care. It usually takes between 5 and 10 years to get a new agent. There are accelerated programs for certain illnesses, for which there's absolutely no treatment, no successful treatment. But except for the accelerated pathways to the FDA, it can take between five and ten years.
Melanie: What’s a protocol? How do people assure themselves if they are interested in getting involved in the clinical trial about the safety and efficacy of a clinical trial?
Dr. Zaia: Okay. The safety of a clinical trial is vested in what we call the protocol. The protocol is actually just the description of what will be done to the patient while they are on the trial. But it is minutely detailed. So we try to anticipate all kinds of problems even if there are side effects. With certain kinds of side effects, we say, “If that were to happen, then you decrease the dose by so much, and if the patient feels sick before the next treatment is given, you delay the treatment until the patient gets over whatever the problem is.” We make sure that their white count is the right low if the treatment is something that would reduce the level of their white blood cell count. Now, the safety of the trial is in the correctness of the protocol and in the ability to follow the protocol correctly. I say that only because when you go to the doctor normally, the doctor is looking after you, but when you’re on a clinical trial, the doctor is looking after the protocol, and he's doing that because that’s the best way to protect the safety of the patient. If he gets offline and starts treating off protocol, let’s say, in the midst of the trial, then there could be problems. There are certainly regulatory problems that the FDA will object to, which you are not doing like you say you'd do it and we approved it according to the exact way that you said that you’re going to do it. So, for safety, we use the so-called protocol, and it’s reviewed and reviewed and reviewed by multiple committees and is reviewed by the FDA, and once it’s finally set, then we begin the trial.
Melanie: You've explained that so well, Dr. Zaia. What are some of the innovative trials going on right now in City on Hope?
Dr. Zaia: Well, the biggest area, I think, for innovation in cancer is cellular type therapy. When I say “cellular,” I mean you take the patient's own natural cells: T-lymphocytes, which are the immune cells; or even stem cells, which are the parent cells for the blood and your immune system. We actually take those cells and we treat them in the laboratory in a certain way to make them more effective, for example, at recognizing a tumour. So, the T-cells are then taken from a patient, manipulated in the laboratory so that they can recognize the tumour, and then given back to you. That's one series of experimental trial and treatments that we have had going. We have stem cells therapy to try to determine if you can genetically make an immune system that's resistant to an infection. For example, AIDS virus-- so we are currently enrolling patients who have had or have AIDS, who’ve even had a lymphoma that's been successfully treated, and we now are taking their stem cells, genetically making them resistant to the AIDS virus and then infusing them back in to see whether or not they would then not only be cured of their lymphoma but also of their HIV infection. There are, of course, new anti-cancer agents. They’re becoming available, and there's more and more of those all the time. I think that what City of Hope offers is access to the latest available therapies. So, we get those from a number of sources: We make some of them here, from our own discovery, but many of them come from the outside, mostly from pharmaceutical industry. The pharmaceutical industry, of course, is very anxious to test these new agents, but we are also very anxious to get the latest agents as well. So about 25% of all of our trials come from the pharmaceutical industry and this gives us access then to agents that have great promise. That is a major reason, I would say, why you should come to City of Hope, if you have cancer, because you then have access to this kind of agents.
Melanie: And how does one get more information about joining a clinical trial at City of Hope?
Dr. Zaia: There are two ways, I would say. There’s the City of Hope website, which is cityofhope.org. When you go to that website, there are a number of things you can go to, but you can go to “how to find your doctor.” But there is also research at City of Hope and you can then look up “clinical trials online,” we call it. It has a Spanish and an English version. You can then put in the type of illness you have (lymphoma, breast cancer, lung cancer) and see what kind of clinical trials we have. Or you can just call the New Patient Office. The New Patient Services is at 1-800-826-4673. That’s 1-800-826-4673. At that office, they can direct you to the right place for your particular problem.
Melanie: Thank you so much, Dr. John Zaia. You're listening to City of Hope radio. For more information on clinical trials at City of Hope, you can go to cityofhope.org. That’s cityofhope.org. This is Melanie Cole. Thanks so much for listening.
Clinical Trials: Life Saving Research. Might You Be a Candidate?
Melanie Cole (Host): The aggressive pursuit to discover better ways to help patients now—not years from now—places City of Hope among the leaders worldwide in the administration of clinical trials. My guest today is Dr. John Zaia. He is professor and chair in the Department of Neurology and director of the General Clinical Research Center at City of Hope. Welcome to the show, Dr. Zaia. Tell us, what are clinical trials?
Dr. John Zaia (Guest): Clinical trials are a test of whether a new treatment is safe and whether it works. Basically two kinds: There are those that we call therapeutic, that is, the intent of these trials is to see whether the treatment is better, because the outcome is to cure better than the standard therapy. The other is called nontherapeutic, in which you’re just trying to find out a better way to manage a patient, a better diet for the patient, whether exercise programs are better for a patient, whether a diagnostic test is better, that is, you can actually determine whether a person is at a low-risk group or a high-risk group if they come in with a new diagnosis. So, in summary, you have a therapeutic trial and a nontherapeutic trial.
Melanie: When we look at the different types of clinical trials, prevention, or screening and detection, are these all parts of it from prevention of a particular disease all the way through quality of life and in the treatment room?
Dr. Zaia: Yes, they involve the full spectrum. How do you assess a patient on the first day that you see him, that is, how do you determine? Can you categorize him into a person that is going to do really well and therefore does not need aggressive treatment or a patient that is going to need more aggressive treatment? All the way through the process to the end, and then you assess: What that this done to their quality of life?
Melanie: So what would be the benefits to being involved in a clinical trial? What patients would be interested in getting involved?
Dr. Zaia: That's a difficult question, and the reason I say that is that certain of our trials are the first time a new treatment has ever been used in that patient; it’s usually for an illness for which existing treatment just doesn't usually work. When we do that, it's so experimental that it may be what we call a first-in-human trial. We have several first-in-human type of trials here, which means that we don't know what’s going to happen; we're really doing this to see if it's safe. We tell the person that we cannot expect a benefit.
Many of the other trials though are in Phase 2 and Phase 3, we call it. So, once you are out of that first phase, we call it a Phase 2 to see how good a new treatment is, and then Phase 3 is when how good it is compared to the existing alternative. When you get to that part of the trial—and I’m talking, of course, about the therapeutic trials—there is a good chance of benefit. We explain that at least they’ll be getting as good a benefit we think as the standard of care.
Melanie: Dr. Zaia, what does it take for a clinical trial to get the Phase 4, to where it starts to be looked at by the Food and Drug Administration and approved?
Dr. Zaia: Actually, Phase 4 is where it’s approved and then you actually use it in its approved agent. You continue to monitor people that are on that treatment. How do you get to an approved drug is what you are really saying. That is a multimillion-dollar question. I say that because it takes so long for the safety trials to be completed and for the trials to determine, what's the best dose of a new treatment? Then the large population studies is when you are actually comparing this to standard of care. It usually takes between 5 and 10 years to get a new agent. There are accelerated programs for certain illnesses, for which there's absolutely no treatment, no successful treatment. But except for the accelerated pathways to the FDA, it can take between five and ten years.
Melanie: What’s a protocol? How do people assure themselves if they are interested in getting involved in the clinical trial about the safety and efficacy of a clinical trial?
Dr. Zaia: Okay. The safety of a clinical trial is vested in what we call the protocol. The protocol is actually just the description of what will be done to the patient while they are on the trial. But it is minutely detailed. So we try to anticipate all kinds of problems even if there are side effects. With certain kinds of side effects, we say, “If that were to happen, then you decrease the dose by so much, and if the patient feels sick before the next treatment is given, you delay the treatment until the patient gets over whatever the problem is.” We make sure that their white count is the right low if the treatment is something that would reduce the level of their white blood cell count. Now, the safety of the trial is in the correctness of the protocol and in the ability to follow the protocol correctly. I say that only because when you go to the doctor normally, the doctor is looking after you, but when you’re on a clinical trial, the doctor is looking after the protocol, and he's doing that because that’s the best way to protect the safety of the patient. If he gets offline and starts treating off protocol, let’s say, in the midst of the trial, then there could be problems. There are certainly regulatory problems that the FDA will object to, which you are not doing like you say you'd do it and we approved it according to the exact way that you said that you’re going to do it. So, for safety, we use the so-called protocol, and it’s reviewed and reviewed and reviewed by multiple committees and is reviewed by the FDA, and once it’s finally set, then we begin the trial.
Melanie: You've explained that so well, Dr. Zaia. What are some of the innovative trials going on right now in City on Hope?
Dr. Zaia: Well, the biggest area, I think, for innovation in cancer is cellular type therapy. When I say “cellular,” I mean you take the patient's own natural cells: T-lymphocytes, which are the immune cells; or even stem cells, which are the parent cells for the blood and your immune system. We actually take those cells and we treat them in the laboratory in a certain way to make them more effective, for example, at recognizing a tumour. So, the T-cells are then taken from a patient, manipulated in the laboratory so that they can recognize the tumour, and then given back to you. That's one series of experimental trial and treatments that we have had going. We have stem cells therapy to try to determine if you can genetically make an immune system that's resistant to an infection. For example, AIDS virus-- so we are currently enrolling patients who have had or have AIDS, who’ve even had a lymphoma that's been successfully treated, and we now are taking their stem cells, genetically making them resistant to the AIDS virus and then infusing them back in to see whether or not they would then not only be cured of their lymphoma but also of their HIV infection. There are, of course, new anti-cancer agents. They’re becoming available, and there's more and more of those all the time. I think that what City of Hope offers is access to the latest available therapies. So, we get those from a number of sources: We make some of them here, from our own discovery, but many of them come from the outside, mostly from pharmaceutical industry. The pharmaceutical industry, of course, is very anxious to test these new agents, but we are also very anxious to get the latest agents as well. So about 25% of all of our trials come from the pharmaceutical industry and this gives us access then to agents that have great promise. That is a major reason, I would say, why you should come to City of Hope, if you have cancer, because you then have access to this kind of agents.
Melanie: And how does one get more information about joining a clinical trial at City of Hope?
Dr. Zaia: There are two ways, I would say. There’s the City of Hope website, which is cityofhope.org. When you go to that website, there are a number of things you can go to, but you can go to “how to find your doctor.” But there is also research at City of Hope and you can then look up “clinical trials online,” we call it. It has a Spanish and an English version. You can then put in the type of illness you have (lymphoma, breast cancer, lung cancer) and see what kind of clinical trials we have. Or you can just call the New Patient Office. The New Patient Services is at 1-800-826-4673. That’s 1-800-826-4673. At that office, they can direct you to the right place for your particular problem.
Melanie: Thank you so much, Dr. John Zaia. You're listening to City of Hope radio. For more information on clinical trials at City of Hope, you can go to cityofhope.org. That’s cityofhope.org. This is Melanie Cole. Thanks so much for listening.