Working In Oncology
Working In Oncology

Episode · 10 months ago

Clinical Trials and the Patient Experience with Thomas Marron


People who participate in clinical trials will joke that they’re a human guinea pig — but they aren’t. They’re receiving excellent care as well as furthering knowledge that will save future lives. 

But what about placebos? 

In this episode, we interview Thomas Marron, Director, Early Phase Trials Unit at Tisch Cancer Institute, about the patient experience for clinical trials for cancer.

Tom shared :

-There are nearly 5,000 different agents in development in the cancer space

-Two new areas taking over the treatment paradigm

-What the 3 phases of clinical trials focus on

-Informed consent, placebos, and collecting samples

-The next 20 years in oncology 

Stay connected with Working in Oncology on Apple Podcasts, Spotify, or our podcast website.

You're listening to working in oncology, a podcast and video show that spotlights oncology practice staff and industry influencers who work behind the scenes to shape the future of oncology. The more knowledge the oncology community shares with each other, the more we all grow. Let's get into the show. Welcome to working in oncology. I'm your host, Alicia Evans. I'm joined today by Dr Thomas Marin. He is a director of early phase trial unit at the Tisch Cancer Institute and an Assistant Professor of medicine at I can school of Medicine. Tom, welcome to the show. Thank you for having me. I am excited about our conversation today. I think a lot of our listeners are exposed to touch points and the clinical trial process, but I think you'll be able to provide a much deeper understanding. I hope to help. So, before we jump in the show, Tom, can you tell our viewers a little bit more about you, your background and what you do? Sure so. Educationally, my background, I have a PhD in immunology and a lot of my work is focused on immune therapies, which are therapies that sort of harness the immune system. To attack cancer and I'm also a medical oncologist, and so I on Fridays I see what I call normal patients, which are patients that are not in clinical trials, and those are lung cancer patients. And the rest of the week I leave the early phase trial unit, which basically is a collection of phase one and two trials that are looking at new therapies that were developed, you know, typically in mice and in monkeys and then and they're putting put into humans for the first time. Well, okay, so you have both sides of a key. Have the reacher side and you also have the patient care side. Yep, I guess a little bit of everything. Great, so there are thousands of oncology therapies in development right. Yeah, Yep. So can you tell us a little bit more about the different categories? So what's new and upcoming that we should be looking out for? So there's a lot upcoming. There's actually almost five thousand different agents that are in development right now in the cancer space. So it's a very exciting space. That's actually almost a problem that we have so many different agents to look at. But, you know, sort of taking a step back when we talk about treating cancer. There's a few different ways to do it and many times we're using what we call multimodality therapies. We're using a bunch of different types of therapy all on the same patient to help improve the outcomes and hopefully improve the cur rates. So obviously a lot of people know about surgery and radiation. The goal of those is to really kill a tumor and get rid of a tumor. But oftentimes, along with surgery and or radiation, will have to use chemotherapy and that's sort of the classic therapy that we've been using for decades. And Chemotherapy is really a bit of an umbrella term that talks about lots of different types of therapy, all of which are kind of, for lack of a better term, poison you know, chemo is a very toxic compound that typically is more toxic to cancer cells, which are growing very fast, and the rest of your body, but it still does have a lot of side effects because it can be poisonous to normal cells, like one of the reasons why your hair falls out or why people might have nausea and vomiting when they're getting chemo. There's also there's two different areas that are really growing fast and are kind of taking over the treatment paradigm for many of our patients. One is an area called targeted therapies, and targeted therapies are really geared towards patients who have a very specific change in their DNA in their tumor or also sometimes in their body. But usually, you know, what makes cancer happen is that you get mutations or changes in your DNA, which is our genetic code that tells cells how to normally divide, and that might be just from bad luck, which is typically the case, or also from things like smoking cigarettes or, you know, lying out in the sun too much and just getting exposed to lots of harmful radiation or chemicals that cause changes in your DNA. So there's certain types of cancer that have very specific change in the DNA that allows us to use a medicine, oftentimes their oral medicines, that ...

...can target that specific cancer cell, and those are nice therapies because oftentimes they're not as toxic to the rest of the body as chemotherapy might be. But unfortunately, you know, we don't really have a lot of targeted therapies yet in our tool box, and so most patients are actually not candidates for that sort of therapy. So everyone else they get, you know, the the standard therapy and the standard therapies for many types of cancer, you know, lung cancer and cancer, bladder cancer, skin cancer. Now includes immunotherapy, and the way that immunotherapy works is it really activates your immune system to recognize the cancer is something foreign and attack it. So your immune system is there to differentiate between foreign things like covid and self things like your skin and your hair and your lungs, and your tumor is somewhere or the patient's tumor is somewhere in between those two. So they weren't born with their tumor. So it is foreign to their body, but it's not as foreign as coronavirus, for instance. But also what happens is that cancers find a variety of ways of putting up stop signs and keeping the immune system at bay, basically hijacking your immune system so that they can't attack the cancer. And so what most of our therapies, especially all the FDA approve medicines that you now see advertised on television like key, true to an up devote. Those are all about tearing down stop signs that the tumor puts up that allows the immune system to then, you know, attack and kill the tumor, and those are great and they really revolutionize the way in which we treat many cancers, especially, you know, today, when we're reporting it's a Friday. I just saw at a lung cancer patients, many of whom are receiving some of those therapies I just mentioned, and many of them are in, you know, dpermissions, and we even have patients that in the past would never be cured of their stage four cancer and now they're actually being cured things to immune therapy. So it's really revolutionize the way in which we treat cancer. But the reason I still have a job and the reason that we have these five thousand drugs that are in development is that a minority, typically somewhere between you know ten and forty percent, of patients, depending on the type of cancer they have, really benefit long term from those immune therapies, and the rest of them, you know, they might initially have a good response, but then unfortunately the cancer out smarts or immune system or out smarts the drugs that were using and is able to grow. And so that's really where you know I come into plays is clinical trials and offering those patients who've most of them were all of them really have already had the standard medicine and then they come and see me because the standard medicine either didn't work or stop working and they want to try something new. So they've already had what step one and then so you're they are alternative exactly. And you know, some patients have just had one type of you know, chemotherapy or immunotherapy, and other patients, like breast cancer patients for instance, often times I've had many different types of therapy because there's many therapies that are effective in breast cancer, and so it really depends on what type of cancer a patient has. That dictates, you know, how soon they might come and see someone running clinical trials such as myself, versus just continuing the standard, you know, FDA approved medicines cut it, and approval of all these wonderful new therapies are dependent on successful clinical trials. Yes, yeah, I always I always try to remind people that, you know, every medicine that they've already received, most medicines we've received in our life, cancer or not, have all been developed using clinical trials the same way that you know, a lot of people have learned a lot about clinical trials recently because of coronavirus. Everyone was, you know, following, made it attention. You know, phase one, two and three trials, and now I feel like people are a little bit more versed in how clinical trials work, but it is it's a complicated field and a lot of questions remain when patients come in and start trials. Yeah, so we are often the guide for our patient in a clinical trial process. Can you kind of walk us through kind of deep level, a little bit deeper at how is the process work and maybe if you could along the way give us some tips for helping to ease our patients through the process? Sure. So, you know,...

...taking a step back just the overview of clinical trials, there's stage there's phase one, two and three trials. There's also a phase four trials, but that's a different thing after something already becomes FDA prove. But so phase one trials, most of the early phase trials are phase one and two trials and those are really geared towards doing two things. Looking A to see if the new medicine is safe and often times what we'll do is we'll do what we call a dose escalation, where we started a very low level and we slowly work our way up, because we don't want to give somebody a medicine, a brand new medicine, that might be very toxic to humans, even though it wasn't toxic to mice and monkeys in which we tried it before. So That's phase one. Trials are really about what we call dose escalations, slowly working our way up in the dose and seeing if it's toxic. At the same in time, you know, we're hoping that we're not having any side effects we wouldn't expect. We are looking to see, you know, is it working or not, is it helping shrink the tumor and what the the next phase, which is phase two, is where we decide what the optimal doses and that's really where we give it to, typically many more patients. So typically that point we do dozen, sometimes hundreds, of patients will give the medicine to it a set treatment dose and will say, all right, is this working or is this not working? If it is working, which unfortunately is a subset, but you know, the for the things that do seem to be working, then we oftentimes will have to do a phase three trial the same way that they did face three trials of the covid vaccine, where they gave, you know, a certain chunk of people the vaccine and they gave another chunk of people a placebo vaccine, a fake vaccine, and they saw who got covid. So that's typically how we do things in cancer. However, oftentimes you won't get there may be a placebo involved, but often times what happens is patients will get whatever the standard therapy is versus this new therapy. So it's not necessarily a placebo. They might just get, you know, a new type of chemotherapy or an old type of chemotherapy right get further something that we would use. You know, if you were in a city that didn't have a clinical trials program that would be what you were offered by your ecologist. It will be that versus, you know, in new medicine and in those phase three trials, which are not things that I run, those are more, much larger trials and they're typically run a different types of senders. You know, patients are randomized, which means that you kind of have to sign on a dotted line commit to doing a trial and then a computer system will assign you to either the new treatment of the old treatment, and sometimes it's blinded and which means that you don't even know, and your doctor doesn't even know, which medicine you're getting. Are you getting the new one or the old one? So that's the final step and getting something FT approve. But what I really focus on is what we call early phase trials, which is phase one and two trials where we're really seeing are these new medicines, you know, toxic, and are they helping people and do they seem to be shrinking humors? So you're at that early stage. So there are certain hiccups that come in for the patient when they are participating in these trials. I know that sometimes navigating like exclusion criteria, that patients sometimes have questions about that. How do you navigate that in your office? How do you what are your best practices for explaining that to patients? Sure, so, one of the most important things when it comes to clinical trials is a informed consent, and that is a process by which we meet with the patient and we go through a very long form that has lots of information about it, about the trial and about all the possible side effects in all the alternative therapies like a chemotherapy or standard therapy, and we go through that and at the end there's a part where I sign them, where the patient signs, and I always really emphasize this with patients, that it's not a contract, that you're not committing your life to anything. What you're really doing is you're it's a permission slip, so you're giving me permission to start the process of screening you and making sure that you are a good candidate for this trial. And at any point the patient can tear up that contract and...

...or that permission slip and say I don't want to do this. So when they sign I always want them to realize that they're still the boss. They're always the boss, even after they start treatment, they're still the boss and they can always say all, I don't want to do this anymore. Once a patient signs a consent for him and we go through the whole thing together, at that point we do something called screening, which is where we do so a lot of tests, oftentimes blood tests, and sometimes we do new you know, cat scans or MRI's or other imaging modality. Sometimes we even do biopsies of the tumor, and that's all done to make sure that the patient fits all of the specific criteria, the inclusion and the exclusion criteria. And so any clinical trial has very specific rules about who can go on the trial and who can't go on the trial. And it's not that we're trying to be mean and exclude people, quite the opposite. We're trying to make sure that we're very inclusive, but that we're not risking people's lives while we're doing this trial and we're not, you know, risking putting people who may be very sick on a trial that may make them even more sick and at that point we don't know is it the new medicine or is it just their cancer that's making them sick? So it's really to protect patients that we have here these very strict rules, and these rules are, you know, one we write a clinical trial. You know, I write a trial, it's typically, you know, a couple hundred pages. We submit it to the government before we open the trial and the Food and Drug Administration has to give their stamp of approval and say that they are okay with US opening this trial and as soon as they give us their stamp of approval, we can open the trial. But we have to do exactly what it says on that piece of paper. And so a lot of the Times patients will say, can't you bend the rules? It's super illegal for us to roll. So we definitely have to follow those inclusion exclusion criteria to the tea. But that really is the most important reason that we do. That is to protect our patients and so unfortunately we can't offer a trial to everyone who comes and sees us. But you know, our number one priority is never the trial and is never, you know, the company making the new drug. Our number one priority is always the patient sitting in front of us. So it's not it's not personal, it's really for the patients protection. Yeah, and also to keep you out of jail important as well, which is pretty important. And so we talked about the consent forms. They're probably long. They're long, they're written in legal he's they're a little bit difficult to understand. They try to write them, they try to write them in simple English. I personally, when I read them, I can barely understand them because I think that they're a lawyer's version of simple English is very different from my versi simple English. So I typically explain everything and then we go through the consent form because I I feel like I'm doing a better job of explaining. Typically, and I think most physicians do that, is that we want to give a patient our idea of what the plan is, and it's also important for me that patients understand the mechanism of how these drugs work and what we think is happening inside of them if they are working, because I think it's an important part of the healing process to understand what these medicines are doing and, you know, what the possible side effects might be, just to really, you know, understand the mechanism that these drugs have to I mean they can make it informed decision. So your tip would be to explain the consent forms and to also give a thorough explanation about the mechanism of the drug. that. Yeah, and they don't. The consent forms unfortunately, oftentimes don't even really go into in depth explanation of how the drug works. It's more here's some possible side effects and here the different you know clinic visits you're going to do, but it doesn't really give a lot of background, which I find to be, you know, important in reassuring to patients to know what's happening in their body and what's going into their arm. So absolutely have been this is thorough content then. And then you also talked about a collecting samples. That's something. So as part of any clinical trial, especially early phase trials, we do a lot of blood tests and we do a lot of blood tests for two reasons. So one, we oftentimes will have people come in, you know, even if you get a treatment only every three or four weeks at...

...first, will often times have people come in at least every week, maybe every day for a week and say you're going to see a lot of meat. So you know, just sort of take that in consideration when you're signing up for something. So there's a lot of visits. And then we do a lot of blood tests and we do blood test for two reasons. One is to check, you know, your organs and make sure there's no side effects with kidney or liver or anything else that we can check on a blood test, which we can't look for everything in a blood test, but we can look for some things. And the other thing is we take a lot of blood for research purposes, and that's because one of the things that we're doing while we're treating a patient in front of us and obviously hoping that, you know, they do well, is we're testing how much of the drug is in their body and how quickly do they metabolize that, meaning how quickly, to hear it from their blood, they pee it out or you know however it's cleared, and so we have to do blood tests at regular intervals and I always warn people the tubes because of this sort of fish I approach. You know, they tubes are all kind of they're all circular at the bottom and the shape is circular, so it makes the tube look a lot bigger than it really is, and so some of these two look, you know, huge and they actually only have the even our biggest tube only has a two thirds of a tablespoon of blood in it. So people will sometimes look at all the tubes I'm drawing and say you're definitely a vampire, and I reassure them that even though I'm a Pale Irishman, I'm not a vampire and we're really just taking the blood for both safety purposes but also for the research purposes. And when I say research, it's really just because we have to go back to the government and say, you know, yes, we are doing what we said we were going to do with this drug and it's working for the following reason. So there's reasons in all those flood tables. Yes, yeah, it's not. It's not for our fun. We reassure people of that, but it's for for safety and also just to be a litle to make sure that we know that we are doing what we say we're doing. Are there any other hang ups or any other but I would say stumbling blocks that come up for patients, any major questions that they have that you run into fairly often. I'd say the number one question that all of my patients have when they walk in the door is about place e vows and if they're getting actual treatment and as part of a phase one and phase two trial. There are never placey vows, maybe in phase two occasionally, but very rarely, and so everyone is getting the drug. There's no sugar pills, there's no fake medicine, there's no blinding. So you know, I know exactly what you're getting and you know exactly what you're getting. But it is important to know. I mean, you know, at Mount Sine I we do have phase three trials and I know a lot of patients are very reticent to go on those trials and I totally understand that. You know, it is the only way in which we can push the field forward, to really test something against a gold standard, you know, kind of the the way it's been until now. That's the only way that we can really have progress. But it is the reality of face free trials that you have to realize that you might be signing up and not getting the real thing. But in phase one and phase two trials, you know you're always getting the drug. We just don't necessarily know if it's, you know, work or not. So that's really the thing counterbalance, because in phase three you might be, you know, in the trials where you might be randomized. Those are the drugs that are most promising because they're most close to being approved, and so you always have to to way that. A lot of people also, you know, they come in and they say, you know, I'm you're just treating me like a Guinea pig, like I'm an experiment, and this is research, these are clinical trials, these are this is an experimentation of sorts, because we're trying new things. But I want to reassure people that were not ever experimenting on patients at their expense. For other people, our goal is always to help the person in front of us, along with helping, you know, mankind by furthering knowledge and and it's important that people realize that. But it is, you know, it is a commitment to doing something new, to taking a medicine that hasn't been proven to work and in whom, you know. We don't know what the side effects are, we...

...don't know who it's going to work for. You are you are committing to a new therapy and so and that's a personal decision that I don't think is fitting for everyone. And I think it's also important to find a doctor that you can trust and that you can connect with and that you know, you feel like, is gonna be looking out for you while you're on trial. Cut It. So the plussy bout question. It's by understating correct that there is no sugar pill and these sorts of trials you would just get the standard, the stand treatment rather yeah, so I might a m trial, as we never have a sugar bill so it's only it's what we call a one arm trial, so it's not like you're getting the new medicine or the old medicine. It's just the new medicine and we might be going up on the dose, so different people get different doses slowly as the trial progresses. In most phase three trials there are occasionally pussy was in. This will be very explicitly laid out in the consent form it lead. For legal purposes they have to let you know there is a sugar bill in here and and it's important to ask questions about that and find out whether it's a sugar pill that is the alternate side, or if it's just another type of chemo or another effective therapy. Because many of the trials were your randomized. They're actually randomizing between a perfectly good therapy, which is the standard therapy from here to China, and that exact same therapy plus something additional, and so those are I think those are great trials. Those are great randomized trials because you're guaranteed to get the same thing that you would get even if you didn't sign up for the trial. It's just you have maybe a fifty or a you know, two thirds chance of getting an additional medicine on top of that that may, you know, further benefit you. So we have many trials like that. It's just important and I'm always happy that people come in and immediately ask that, because that's, you know, something that I think it's important that people know is the design of the trial. So, you know, are there multiple arms? Are there, you know, different treatments that you could get based on a computer, based on, you know, the design of the trial. It's important to go into it with your Eyes Wide Open. And then that goes back to thorough reading an explanation of the content forms. Yep, yeah, and I always, you know, we always give a copy of the consent form after, you know, we go through it with them and we both sign it and then we give them a copy to take home and I always get people, you know, my my phone number and I tell them to email me or call me after they've read it if they have questions because, as I said, sometimes they're rewritten by lawyers that make things less simple than they should be. So it's important that people know what they're getting into. And I've definitely been the situation where I've gotten home and reread something and said, I know I have questions about this. I would also if I read some of these things. That's right. So I always go through with the patients so that you know, I can point out very confusing parts of it that we did talk about. These mention. Do you say five thousand? Yeah, you therapies. Yeah, it's an exciting you know, cancer is scary and there's no good time to get cancer. So it's always kind of a cliche to say this is a good cancer to have or this is a good time to get cancer. But you know, the way we treat for instance, Lung Cancer Right now in two thousand and twenty one is radically different than the way that we would have treated it in two thousand and fifteen. And you know we are in two thousand and fifteen. If you had stage four lung cancer, there was a near one hundred percent chance that you would die of that cancer. Now, you know, we're carrying probably twenty to thirty percent of patients with lung cancer, which is extremely gratifying and it's why I love my job and I was coming to work, particularly on Fridays when I see my lung cancer patients. But we you know, we still have a lot of room to grow. You know, twenty to thirty percent is not a hundred percent and a hundred percent is obviously the goal here. But it's exciting seeing, you know, these five thousand agents that are in development and we just had, you know, one of our big conferences last week and that we saw, you know, really rapid progress on many exciting new drugs and I think that it's a very exciting time to be an ecologist. And, you know, any every time that we get a new...

...medicine that further prolonged people's lives, it does two things. One, it really obviously keeps people alive longer, but it also keeps people alive longer so that a year from now, when we have additional progress and we have additional DU drugs, we're going to have a whole new option for them. So, you know, it's oftentimes we may not be curing people, but we hope that we are at least, you know, prolonging their life until we do in fact have a real cure for them. And I like to kind of end my podcast on a happy note and a little bit of hope. So do you have any predictions for the future of oncology therapy predictions, but do you imagine for the future? What it well, what will it look like in twenty years? So I do in in twenty years. So one of the a lot of the work that I do in in the laboratory with my laboratory colleagues, which are right outside my office. We, you know, we take a lot of those blood samples that we are are getting from patients that we bring them up to the lab and we we're studying them because we're really trying to understand what is it specific about the patients that are doing really well versus those that don't have a great response. And one of the goals of that therapy is really to develop personalized medicine. And personalized medicine is a catch phrase. You hear it a lot in every field of medicine. But the goal, you know, hopefully, you know, twenty years from now we're going to be able to do a biopsy of a tumor and we can do, you know, a biopsy of your blood or just to draw of your blood and we can basically look at your immune system and look at your tumor, which both those things are completely unique. So everyone and who I've ever seen as a totally unique immune system and a totally unique tumor. In the future, I hope that we can biopsy both of those and basically use an algorithm to predict exactly what the optimal therapy is like how we can specifically treat them the best to get them the best clinical outcome and also the least toxicity possible, because some of these drugs do have side effects. So I think that we're already inching in that direction with the you know, I mentioned the targeted therapies where we are identifying these very specific changes in genes, but I think twenty years from now it's going to be a radically different landscape where we really will be able to offer people, you know, personalized approaches that, you know, optimize their care and give them, you know, the best quantity of life and quality of life. That would be incredible, amazing stuff coming up. So Tom this has been such a great conversation. If any of our listeners want to reach out to you for any follow up questions, what's the best way for them to do that? Sure email is always the easiest for me because I'm never picking up my phone, so I'm patient. Email is Thomas Thomas Dot Marin, m a R R N at MSSM DOT Edu. It sir, amount sign at email so people can feel free to reach out to me with any questions or any concerns with clinical trials. Definitely Great. So what I'll do is I'll just include that in the show notes. Anyone could reach out to you Tom Again, I want to thank you again. Thank you for joining us here and working in oncology. It's been a pleasure. Thank you. Are You satisfied with your patients curtsy to therapy, or are you just settling? You can improve patient outcomes with bioplus specialty pharmacies power of two, the first ever two hour, two day to gather promise. It's faster and easier for you and your patients to learn more. Visit bioplus R xcom. You've been listening to working in oncology. To ensure that you never miss an episode, subscribe to the show in your favorite podcast player. If you're listening in Apple Podcast, we'd love for you to leave with rating of the show. Just have the number of stars you think the podcast deserves. Thank you so much for listening. Until next time,.

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