Clinical trials demystified, part 1: Adrian Terek (2021)

Manju George 0:02
Hi everyone. I am Manju George, the Scientific Director of Colontown. As you know, I have been bringing DocTalks to you, where we have experts from the medical field talking to us about colorectal cancer trials, about radiation therapy, about immunotherapy and all of that. So while I was talking to Julie, who we have with us today, she had this idea of, what about from the patient and caregiver side, how about getting some experts who have experience with clinical trials, and what if they told us their experience and what they have learned? So that is what we have today. And Julie, do you want to introduce yourself and tell us more?

Julie Clauer 0:41
Sure. I’m Julie Clauer. I’m on the Colontown Cabinet. I’m also a Stage IV patient who was in a clinical trial. And when I heard about Monju’s DocTalk I was so excited, because I was like, Oh, that’d be so great. We can hear about these trials and then we understand them. And then I was like, but you still have the issue of, how do I get into the trial, and how do I figure out if that’s right for me, and that’s a lot of the piece. So I thought if we had patients and caregivers provide that perspective to help navigate through, it would be really meaningful and powerful. So Manju and I started thinking of people that could be involved, and there’s a lot of people within Colontown we think bring really good perspective from their experience in clinical trials. But there’s also patients and caregivers outside of Colontown that have much broader experience in other ways. So Manju, why don’t you introduce our first guest?

Manju George 1:27
Yeah. Okay, so we have Adrian Terek with us. Welcome Adrian.

Adrian Terek 1:32
Thank you for inviting me here today. I appreciate the warm welcome. My name is Adrian Terek. I’m the founder and director of Life Trials, which is a charity that is focused primarily on highlighting the latest research so that patients can be informed about clinical trials. The idea is to make it as easy as possible for patients to learn about the biggest changes that are happening in their cancer type, and what promising trials are out there, and how they can access them. Like most people, cancer has touched my life in one way or another. When it comes to being an advocate, it popped up because my mother was diagnosed with early stage cervical cancer. At that point, I had been lucky in my life. I’d never had someone near and dear to me be diagnosed, and so we were very reassured by her doctor. They had caught it early. They showed us the statistics for the chances of the surgery and radiation to essentially cure her. There was like 92% chance that she was going to end up cured. So we just took it day by day. I was not an advocate at that point. I was just a supporter of my mother while she did what she had to do to kind of get to that point and when it came time for her first scan to see whether it had resolved, instead of being in that 92% she was in the 8% where it had metastasized throughout a lot of her body. And so she immediately became Stage IV, and that’s when I looked up the statistics for what that looks like with cervical cancer. And the statistics are very bleak. Simply put, cervical cancer is a hugely unmet medical need. There’s essentially no good therapies once you’re Stage IV. And so the conversations with her doctor changed very quickly to, we can do these chemotherapies, but they probably don’t work very well. You should get your life in order and enjoy the little time you have. And at that point, I immediately switched from just being an emotional supporter for my mother, to an advocate. It then became okay that this is simply an unacceptable truth. At the time, that’s the way I viewed it. And I had a very basic understanding of things. I just thought to myself, how come I keep reading about these breakthroughs here and there on the news? And then when it comes to my mother, they’re saying, yeah, the only thing we can offer is a 25 year old chemotherapy that also doesn’t work at all. I couldn’t square that circular peg, right? So essentially, I just started reaching out. I started reaching out to doctors and researchers around the world who are specialists in cervical cancer, who would then say, I’m not your guy, but talk to this person here, and then they’d connect me with somebody else. And over the course of a few months, I essentially went from knowing barely anything about cancer at all to being aware of all of the most pertinent research, who was conducting it, where it was being conducted, what kind of results they had been seeing. And I went back to my mom’s doctor and brought up some of these results, and she said she hadn’t heard of them. And that was my first experience in the limitations of knowledge dispersion, right? There’s so much information being generated, and doctors are busy, so it’s hard for them to keep up with all of it. And so that was a big shock to my system. When I’m like, How come I know this and the person that is entrusted with my mother’s life doesn’t know this? And so at that point, we essentially took it upon ourselves to kind of manage her care, right? At that point, the chemotherapy was not really working, and we weren’t really given other options, and so we had to essentially do it on our own and through all of those experiences, that’s essentially where Life Trials came from. I said there has to be a better way for patients to learn about the exciting research and make the connection of where they can access those treatments and how to connect to it and so I essentially set out to build the tool that I wish I had. I had to feel my way in the dark that entire time, and the goal of Life Trials is to make it so it’s a one stop, you create an account, you answer some questions, and it just walks you through, A, B, C, D, E, so you immediately are up to date on all the important stuff, and can start making important decisions.

Manju George 6:14
How did you first learn about clinical trials?

Speaker 1 6:17
You start looking on just generic cancer websites and they’re constantly saying, clinical trials are a good option, but theydon’t help you figure out which clinical trial is a good option. They just say this generic, a clinical trial is probably good but I wasn’t interested in my mother doing a clinical trial. I was interested in my mother doing the best clinical trial, and so that’s where the real legwork came in. Was okay, once you realize that the standard treatments are no longer going to be offering you benefit, then inherently, the only other option is to either stop treatment or do nonstandard treatments, treatments that are currently going through testing. And once you dig into that hole and you realize that there’s 4000 treatments being tested in various combinations, how do you possibly decide which one is the right one? And, in my experience, I asked my mother’s doctor, and she didn’t know, then suddenly it’s like, okay for even her doctor doesn’t know what the most promising trial is, how do I do this? And so I had to learn the hard way through accessing clinicaltrials.gov and then learning how to access the various conferences and read clinical trial posters and understanding what the data means and how to interpret it. It was a very big journey to undergo and with, with Life Trials, again, the whole purpose is to simplify it. There’s, there’s 1,000 things that you could learn, but to be effective in learning about clinical trials and decision making for your treatment, you can reduce that down to only learning 10 things. And if you learn those 10 things and put it into use, you can get from A to Z quite quickly. Whereas me, I had to do it the long, hard way.

Manju George 8:09
Can you also tell us a little bit about your mother’s journey and how at different points, you realized different things about clinical trials, right? Do you think you’d be able to summarize and tell us quickly?

Speaker 1 8:22
Yeah. I mean, when it comes to clinical trials, there were so many hard lessons to learn. The most difficultlesson was that it took me time to become an effective advocate, right? When you start off barely even understanding what cancer is, then you have to learn about clinical trials, the different treatments in the clinical trials, how they’re evaluated, how you find that data. All of that took time, and time is something that cancer patients are always going to struggle with. And so in this instance, with my mother, we identified four very promising clinical trials, and the very first one was at the NIH. It was a T-Cell trial at the NIH that had published results six months earlier where they had actually cured some patients with metastatic cervical cancer, which is for all intents and purposes unheard of. So this is a very striking result. We got her over there to be assessed if she would qualify. And she did qualify. They said, you’re a great candidate. It takes us about a month to get the T-Cells ready for us to do the procedure, but we have to note that, because of the metastases in your lungs, your lung function is borderline for entering the trial. As of today you qualify, but we need to hope that it doesn’t get worse before you come back a month from now. And so we went back a month later, and the cells had grown. They said they were ready to move forward. They tested her lung function and said, unfortunately, it has progressed to the point where you no longer qualify for the trial. And so immediately my thought was, well, if we had just found this trial two months earlier, she would not have gotten to that point in her progression and her lung function would have continued to qualify her. But because it took me all those months to figure out that this was even an option, let alone the best option, she lost that possibility, right? And that’s hard for me to think that. I’m not suggesting it’s likely she was cured, but people had been cured with this treatment, and she could have undergone the treatment and was denied because of a loss of time. And it kind of got worse from there. So we came back from the NIH, and I said, okay, we have these other three trials that are very promising. And so we called the second trial and they said,oh, we filled up yesterday, so they had basically run out of slots the day before. Once again, time. If we had learned about these trials three months earlier, then she would not have lost out in the second possibility. So we called the third best trial and they said, oh, we filled up this morning. And so over the course of two days from leaving the NIH and being told no to calling these two other trials, she lost the three most promising trials that were available to her, and all of that could have been circumvented if she had just known about them earlier. And that’s an inherent flaw in the cancer patients journey. That’s the issue that Life Trials is there to address. Time is not on your side. Information overload is a problem. It’s so big that even doctors barely keep up. How do we get patients to be able to very quickly understand their situation, understand their options, and be able to start pursuing those options as fast as possible, so that what happened to my mom doesn’t happen to them. Interestingly enough, we got into the fourth tria, so that one hadn’t filled up, which was nice, and it worked. So she, at that point, was probably a few months away from dying, she had progressed quite rapidly. Again, cervical cancer is not a very good cancer to get. Not that there’s any cancers that are good to get. This one’s particularly bad. And by her second injection of this immunotherapy, she had gone from being bedridden to living a regular life. And by her third injection, she was back to playing sports. It was unbelievable to see her go from bedridden to functionally normal over the course of four months. And unfortunately, the treatment did stop working over time, but we easily got another year of healthy quality life with her, and this was the fourth best trial that we identified. The other trials that we identified that were potentially better than this, many of them were combination trials that included the drug that she ended up getting on. And the data at this point does show that the combination drugs are significantly more effective. So if we had not lost out on the first trial, there’s that small possibility she would have been cured. If we hadn’t lost out on the second and third trials, then it’s likely she would have experienced the same benefit that she did on the fourth one, and then some more, because of the potential of the combinations. And so I got to see all the spectrums of what happens in this journey with my mother, the loss of hope when you lose out on the best trials, and then even the benefits of potentially finding a trial that helps you and gives you more time with your loved ones and healthy living. I got to experience that entire gamut. And so I think it kind of prepared me quite well to to try and help people kind of navigate the these difficulties and these promises.

Julie Clauer 13:49
I was just going to ask about his experience, because it’s really interesting. You talked about the four trials you found for your mother, and you very much had a clear ranking. And I think getting to that clear ranking is kind of hard sometimes, so I’d love to hear a little bit more about your process in terms of, how did you decide what criteria to use to rank.

Speaker 1 14:08
That’s a great question. I can simply say that, of course, every patient with cancer, their goal is to just be cured and move on with their life. That’s unfortunately not the reality that often. I am a very strong advocate for looking at your situation with clear eyes, right? Hope is infinitely useful, but blind hope can make you potentially make poor decisions. I definitely have experience with other patients that I’ve worked with who essentially lie to themselves about where they’re at, and that means that they don’t potentially take the steps that will actually help them, live a better life. In this instance, with my mother’s cancer, the outcome was very bleak with the standard treatments, and so I was lucky enough to talk to some of the top researchers who pointed me in the right directions, including the data. And so the way that we ended up kind of creating this ranking was I spoke with my mother and said, what are the goals that you’d like to work towards, right? All of these treatments, by definition, are experimental. If we knew that they worked very well, and for a lot of patients, then at that point, they’re no longer experimental. They’re actual, just treatments. So we looked at sort of what her hopes were, and we identified the trial at the NIH as the most promising, simply because it had, again, cured some patients. And so from my mom’s perspective, she would rather take a slightly longer shot and hope that she would be one of the people who has an exceptional response, than take a drug that may work for more patients, it might work for 75% of patients, but when it works, it works for a few months, right? So her goal was to kind of go for the home run, as opposed to the safe but probably only get you to first base. And that’s a personal question that cancer patients have to ask. You do have some treatments that have a very high response rate. The majority of patients who undergo the treatment have their cancer shrink, but the amount of time that it shrinks for is often very short. And then there’s other trials, like when the immunotherapy trials first started popping up, 6/7/8, years ago, the reason they generated such excitement was because they weren’t working for very many people, they hadn’t figured outwhat markers they could use to identify the patients that were going to do the best, but all they knew is that when they gave it to 100 patients, there’d be five or six of them who would watch their cancer melt away, and it would last for years. And so it is really up to the individual patient which type of trial they’re comfortable pursuing. If they just want something that’s going to give them a bit of extra time and is likely to work, then there are definitely trials that have that sort of data that suggests that would be the more likely outcome. And then there’s definitely other treatments that some of the data is for most people, this treatment doesn’t work at all. We don’t know why it works for some people and why it doesn’t work for others. That’s where the the learning and the the science comes in. But as of now, we don’t know who it’s going to work for and who it’s not. What we can say is that for the few people it has worked for, it’s worked exceptionally well and for significant periods of time, and so that’s where looking at the data with clear eyes and understanding what the implications of that data are, is how you make optimal decisions.

Julie Clauer 17:53
That’s really helpful, because I do think it does take you knowing what you want for sure. So you described that perfectly well. An interesting thing, I think, also is that people assume that clinical trials are going to be riskier than standard of care, and at one point in my treatment decision, we had to decide a new treatment, and one of them was standard of care, and one of them was a clinical trial, an my oncologist said, this one has a 30% chance of working, and this one has a 30% chance of working. We don’t know what 30% you’re in. And so the reality is, for me as a patient, they were equally as risky. And so I think that theory that if you go into clinical trials, you’re going into riskier territory, not necessarily, as we see with all treatments. You know, every individual patient responds differently. So I think that’s something that was super eye opening for me. And if you know your own goals, then you can kind of try and navigate how that fits with what your goals are.

Adrian Terek 18:50
I agree completely, and you just you kind of rung a bell in my mind, that I think is one of the key takeaways with Life Trials. When I talked about my mother’s goals of care, one of the reasons that we ranked the NIH trial very, very highly was not just the fact that it could be that home run that cured her, but the interesting part about that trial was it was not a continuous treatment. It was a one and done treatment. Now some of those treatments do exist, and so when you start to say, okay, statistically, I have eight months left to live, and so I can go and do any one of these four trials, the correct answer is, actually you might be able to do two or three of those trials. And so what we thought about with the NIHtrial was, yes, it’s not likely to work, but it only takes us six weeks to find out. You go there, you get the treatment, and it’s either going to demonstrate that it’s going to have a strong effect on you or it’s not very quickly. And then from there, you’ve taken that shot, tried to hit the homerun, potentially missed, and you still have time to pursue another trial. If she was much further along in her progression, then maybe she would not have selected that because a sure thing that gives you an extra six months might be more important or a better choice than that home run. But I think that what happens with a lot of patients and doctors as well is they don’t frame the question in a logical way when it comes to whether you should participate in a clinical trial and which one you should do. As an example, a lot of doctors, I believe, when they bring up trials with their patients, they’re working on some implicit assumptions, like, my patient will not be willing to travel to get this trial. Now that might be true if the idea of the trial is to go there every week. But again, there are many trials out there that are a single trip for six weeks, and you find out whether it’s working or not, and then after that, you’re out of the trial and you’re no longer traveling. So the question is not, is this patient going to be willing to travel every week for the next four years? Is this person willing to travel for a short period of time to find out what’s happening. And even when you take into account the idea of this person’s willing to travel every week to do this clinical trial, I would actually suggest there’s two questions there, and they might have different answers. So the first question is, is this person willing to travel every week for the next three months to undergo this trial and see if it’s working? If it’s not working, then they no longer have to travel. They’re out of the trial. So the question is very specific, three months worth of travel time, not a lifetime worth of travel time. Then if the treatment is working, well now the question has fundamentally changed to is this person willing to travel every week to stay alive, right? And that’s also a very different question that people will have very different answers for. And so I think that the way that these are framed is really important, and a lot of people don’t look at it from a logical perspective. I think that traveling when it comes to clinical trials is severely underutilized, because the initial question is actually quite simple, are you willing to do a bit of traveling for a few months to see if this works? And I think the answer that most patients would give is, yeah, of course, I’m willing to do that. Then if it is working, then the question becomes, are you willing to keep traveling to stay alive? And again, I think that most people will try their best to find a way to do that, because it’s now a treatment that’s working, right? It’s no longer a question of, am I going here and just flipping a coin? It’s no, I flipped the coin, I guess, right? It was heads, and I got heads. This is great. Now I just need to figure out how to keep doing it.

Julie Clauer 22:30
Yeah, that’s great. Well, I think you raised a good point, because I think the reason why the questions are framed that way is that the person asking the questions has a different objective, right? They’re thinking about the trial maybe, I mean, not that they don’t want the patient to do what’s best for them, but they’re thinking about enrolling people in a trial, and that trial has certain objectives. So can you talk a little bit more about kind of, maybe some of that those things that might be a disconnect between patients and investigators, and how those can kind of be understood a little better by patients to make better decisions.

Speaker 1 23:06
You know, universally, this research is being done because people care, right? The doctors care. They want to help people. Of course, the drug developers want the benefit of helping people and making money at it. But in the end, the goal is, I think, still the same. The goal is to find treatments that help people live better and live longer. But how you go about doing that sometimes can lead to sort of conflicts of interest between what the the goal of the patient is and what the goal of the trial is, rght? There’s a lot of talk out there about very strict inclusion and exclusion criteria for trials. And some people justify by saying, well, we need to have very controlled criteria for who gets into the trial, because we don’t know about this treatment. And so we have to take the healthiest people to make sure that if side effects pop up, they’re the ones who are best able to handle it. So the argument is they’re doing it for patient safety. The other side of the argument is that they use these very strict criteria because it increases the chances of the treatment working, which means the numbers look better than they would in the real world, and it allows them to get approval and start marketing their treatment. I tend to lean towards the second side. I think that a lot of it is that they’re doing it to try and make the numbers look as good as possible, whether that translates into the real world or not. And the unfortunate side effect of that is that with many treatments, you end up seeing that the patients who don’t qualify for a trial because of the very strict criteria, they end up being the kind of patients who also benefit from these treatments. As these drugs then go through the approval process, and they start getting real world data, they start to see, oh, even patients who are much more sickly still got benefit from this, and so we didn’t need to exclude them from the original trial. So, my view is that, yes, they’re working towards the same goal, but I think that researchers are looking at it from a we’re trying to collect data to achieve an objective of proving that this drug works and then getting it approved. And patients are simply doing a trial because they want to get better. And on occasion, that can lead to some discrepancies on how people view things. So as an example, I’ve talked to numerous patients who one of the worries they have about a trial is that once they’re in the trial, even if they leave the trial and it’s no longer working, they’re still expected to go back and, get blood tests every six weeks for the next two years. Controversially, I tell them, don’t let that influence your decision. You don’t actually owe this to them, right? The exchange that I see that occurs in clinical trials is simple. A patient allows a researcher to learn about the effectiveness of a treatment from them in exchange for potentially helping the patient. The moment that it’s clear that the treatment is no longer helping the patient, then the patient has met their obligation, and they don’t have to continue doing those things and I think it’s important, because, like I said, I’ve had patients who I’ve talked to who have almost avoided a trial, because they say even when I’ve dropped out of this trial, they still want me to go back every six weeks and do more tests and more blood and all this stuff. And I just go to them and say, You don’t owe that to them. If you feel like they’ve helped you and you want to continue to contribute, that’s absolutely fine, but don’t decide to do or not do a trial based on meeting some sort of additional criteria that they would like to get. So that’s a bit of a controversial statement. But I think it’s more important that patients get into trials than be the perfect patient within that trial once they’re there.

Julie Clauer 27:09
To your point, though, in addition to after the fact that it didn’t work, but even when you’re on a trial, it’s an at will situation. The patient, even though you have signed a consent, at any point, the patient can say, I’m done. So even if you go into it obviously with the best intentions, and if it’s working, you hopefully want to stay on it. But if you are in a situation where you’re traveling and then you realize it’s not working for you or the side effects are too bad and you still can technically stay on the trial, patients can always say, I’m done and be out of the situation. It’s your body, your life. So I think that’s an important thing too, not that most people make any decisions like that, but I think a lot of people feel like the minute they sign a consent, they’re going to be stuck for life. And the reality is, you’re never stuck. Just like a job. You always could quit a job. Are you going to quit the job? You know, willy nilly, no, but you’re at will. You can decide to do that or not. You’re not obligated.

Manju George 28:07
One of the things I tell people that I talk to is that, before they consider any trial, one of the important things to remember is that, do they have any ways, any good ways, to know how their tumor is reacting to it, right? Is CEA a good marker for you? Is CA 19-9 a good marker for you? Are you going to just rely on scans? And I also tell, like with the BRAF group that I work with a lot, I tell them, is it possible for you to get a liquid biopsy on the side outside the trial? Would that make you more comfortable? Because the key would be that anytime you feel that it’s not working, you can get out quickly. You don’t have to wait until the next scan. Or, you know, if you don’t feel well, like if you have new symptoms, then obviously something is not working, right, which is not the side effects. So I think that you’re more safer getting on a trial if you have some ways of finding out how it’s going for you. But if you’re kind of blind, you don’t have good markers, and they’re not going to give you results, and you have to just wait for the three months scan, then things become a little bit more risky,

Speaker 2 28:12
Absolutely. I mean, in the end, knowledge is power, right? And so the more information you can have about your own treatment and ways to figure out whether that treatment is being useful for you, the better decision you can make. That’s why I believe that sharing the bad data is just as important as sharing the good data.

Manju George 29:29
They have these targeted therapies against specific mutations, or fusions or things like that. Mostly it’s about mutations.So initially, when they’re testing the drug, they have all comers, right? They have metastatic CRC, everybody who has failed three lines or two lines are getting enrolled. But then overtime, you know that it only works, actually, if you have that mutation. So I’ve seen in Colontown somebody coming and saying, Hey, my oncologist told me about this trial. What do you guys think? And the first question that we asked them is, do you have this mutation? It seems very surprising to me that that patient has not even considered that thought, that before they get on that trial, it’s so important to find out if they have the mutation, right? And, I mean, it’s not bad in considering that they could say, Yes, I’m interested. Let’s have a biopsy and find out if I have the mutation, and if I have the mutation, good, I’m getting on the trial. But if I don’t have the mutation, then why in the hell should I get in that trial, right? I feel that patients should have that knowledge to ask that question. And I’ve seen these kind of trials, and in research, we say “have reagent, will test,” right? So it’s almost like that, have targeted therapy, have a trial. So come on, patients, we’ll get you on this. So I think that in our quest to make patients get on trials, it’s very important for people to understand what trials are good and what trials they should not get on. I mean, it’s not a question of not getting on. It’s to find out if they are the best fit for the trial and if that trial is going to be the best fit for them, right? Yeah. I’m so glad we are having these conversations, because I think that through these discussions, a lot of things are coming to light. So thank you.

Speaker 1 31:09
This is what’s so interesting about especially the new era of precision medicine, is that there’s sort of two sides to that coin. On one side, you have some of these highly effective treatments that are effective in quite rare mutations and fusions. So the poster child for this is Larotrectinib. It targets NTRK fusions, which do occur in most cancer types, but at very, very low incidence. So you get this conundrum where if the average cancer patient says, do I have this fusion? The answer is just no. But if you test 1,000 cancer patients, you will find one who has it. And if my mother was that cancer patient who had this fusion, and there was a highly effective drug for it, would I want her to be tested, of course. And so you have this problem where you have this highly effective drug in a very rare amount of patients, and so lots of patients don’t get tested for it, and even the ones who do have it never know that it was a good option that could have given them a lot more time. And on the flip side, you have a bunch of drugs that are targeting different mutations, and just because a drug targets mutation doesn’t mean it’s going to be useful. A lot of mutations are not driver mutations. They’re not responsible for the cancer growing out of control. And so, you run into this problem where a lot of patients get genetic sequencing done, and they get told that they have a mutation in this gene and a mutation in this gene. Hereare drugs that target this gene, but we’ve seen the results of those drugs, and the results are trash. So, yeah, the drug targets that gene and it blocks the the proteins that that gene is coding for, but it doesn’t help people. And so that’s the key. Again, the data will set you free. Is this gene relevant? And then, is the drug that targets that gene effective? And you have to have both of those be true for it to be useful. And so I’m actually not a believer in patients just getting a genetic sequencing done, and then just targeting whatever mutation happens to pop up. Because when you read it pretty much every clinical trial result, as I have for the last seven years, and you see that the vast majority of those results are, we have a drug that targets this gene and it didn’t work. We have a drug that targets this gene and it didn’t work. You start to realize that that paradigm is not inherently the correct approach. It’s still required that you show that the mutation is relevant and that the drug is effective against it. And again, like I said, back to Larotrectinib, even when you do that, you run into the problem of patients not knowing that they have that mutation. So one of the first things that I talk about in pretty much every report on on the Life Trials website is this drug. Because I believe that pretty much every cancer patient, if you went to them and said, there’s a drug, and it works on this fusion, 1 in 1,000 people have this fusion, you could be one of those 1 in 1,000 and if you do have it, this drug will probably keep you alive for a few more years. Would you want to know if you have that fusion? I have never asked that question to someone, and they’ve said, No, I don’t want to know. Right? And so it blows my mind that this isn’t even happening, right? And that’s again, knowledge is power. That’s why Life Trials is there to help people learn about these things and make those decisions, like going to their oncologist and saying, Hey, I heard about this. I know it’s unlikely, but I want to get tested anyway.

Julie Clauer 34:44
So yeah, I think you just hit on a really important point too, because I think a lot of people are like my doctor, they’re so smart and so great, and how would they not know these trials? And how do they not know this? And what you just did I think, helps explain some of that. If you think of the thousands of trials, and the thousands of little things that need to be known about those trials, and then everything about a patient, if you think about that, really the only patient in your doctor’s practice that’s like you, is you. And so it’s not that they’re not smart, it’s not that they’re not aware. It’s just how in the world would any doctor be able to know all of this information about trials, all of this about every single one of their patients. It’s really overwhelming, which is why it’s so critical that patients are the expert on them and what could maybe work for them, and then they can come to their doctor, who’s an expert on other pieces of it, and come together to figure out the whole picture of what could be best for you. Because I think sometimes it’s like how would my doctor not know this? And it does not mean your doctor is not amazing and wonderful and smart. It’s just there’s no chance they will know this, especially with more than one cancer.

Speaker 1 35:55
You hit the nail on the head there with the dealing with more than one cancer. The vast majority of oncologists and the vast majority of patients are not treated at the ultra specialist level. They’re treated at sort of local community cancer centers where that oncologist will see one patient with renal cell carcinoma in the morning and then a patient with cervical cancer in the afternoon, and then a patient with lung cancer in the late afternoon. So that person, the idea that they’re going to be up to date on the 4,000 drugs and combinations being tested in clinical trials right now all across North America and the results of all of those for all cancer types is completely unrealistic. The intention is not to blame doctors, right? There’s just so much information out there. There has to be a solution on how to to curate it, so that people with limited time and limited understanding, like patients, can figure out what are the 10 things they need to know, right? There’s a thousand things out there that they could know. Someone else like us went through it, found the 10 that were the most important, and said, If you just need to know 10 things, these are those 10 things. And here’s what you can do with that information, go ask your doctor about being tested for this. If you have this, talk to your doctor about this. Ask your doctor about this trial here, see if you qualify. Ask your doctor about this mutation here, maybe get tested for that. And it’s a quick checklist to essentially make sure that the most obvious things, that the patients are at least staying on top of that. Many treatments that are showing promise are also available in expande access programs. And so we not only when we inform the patient about the results that kind of are known about this treatment, and show them the trials that are recruiting for that, but we also specifically note this treatment is available outside of a clinical trial. There are ways to access this without having to qualify, and so that can also really be a boon to patients who maybe won’t be able to travel as easily, or might have some sort of issue with qualifying for it. And I’ve been kind of amazed, as I’ve been working on Life Trials over the years, how many promising treatments are available outside of a trial. And so that’s another thing I think that doctors and patients both need to know more about, because it’s truly a lifeline to gain access to some of these promising treatments. And it doesn’t have to throw your life for a complete loop in terms of travel or inclusion/exclusion criteria.

Julie Clauer 35:56
If you see something that us promising, what is it that grabs your attention?

Adrian Terek 36:55
The data is always going to be what sort of guides the decision making. So there’s going to be outside factors that I’ll touch on in a minute. But in the end, you’re just looking at how often does this drug work? So when they test the drug on50 people, did it have a positive effect on their cancer on 10 of those people, or on 40 of those people? The next question is, how long did it work for? You can get these drugs that work for 40 out of 50 people, but they only work for three months, and other drugs that work for 10 out of 50 people, and they work for a year or two, right? So again, those are technically both good drugs, right? The real question is what is the goal for the patient and what are they hoping to accomplish? What’s their risk tolerance? The other thing is outliers. So outliers being when you see a result that happens in a patient or some patients within the trial that is significantly outside the realm of what you normally see. So going back to my mother’s example, with metastatic cervical cancer, the pivotal trial for the current and only real standard of care, first line therapy, every single one of the patients in that trial was dead within two or three years. I can’t remember the exact number. It’s been a while since I looked at it. And that was like a 1,300 person trial, right? So, pretty much universally fatal and quickly. So when you suddenly see the results of the trial at the NIH, it was tested on nine people, that’s statistically not going to tell you a lot. They don’t know exactly why it worked for some of those people, but two out of the nine people were cured. They’ve been following them for the last five to seven years now, and they have no cancer. So if you have the pivotal trial with 1,200/1,300 patients, and all of them were deceased within the first few years, and you suddenly have this, yes, it’s a small trial, but the results of some of the patients was so outside the bounds of what you normally see that you have to sit up and pay attention to it. Now is that the right trial for everybody? Probably not, but the fact that that happened for those two patients means that something interesting is going on with the way that that treatment functions. And so those are another thing that are worth paying attention to.

Julie Clauer 36:55
A big myth or concern people have is around being on a placebo. So, I’m going to be the one that’s put on the part that doesn’t work. Can you talk a little bit more about that?

Adrian Terek 41:13
Yeah, of course. So like you used the words that hit the nail on the head when you said myth, because the reality is, it’s unethical to give anybody a placebo if there’s knowledge that there is a treatment that has already shown efficacy. So in the cancer world, almost universally, placebos don’t exist, unless you’re unlucky enough to be in a patient population where there is no other treatments that are showing any sort of benefit whatsoever. But what often happens is the treatment is actually being compared to the current best treatment that is part of the standard of care. So WI’ll use my mother as an example. When she became metastatic, they suggested chemotherapy for her. That was the current first line standard of care. She could have joined a trial where they would have randomized her to one of two options. I do want to note that patients should consider when they’re joining a trial, if they don’t want to get the standard of care and they want to get the experimental treatment, and it happens to be that that trial is a randomized trial, and they’re not sure which one they’re going to end up on, they should really also spend some time looking for other trials that don’thave that. Not all trials are randomized, and so some patients would actually rather go on a trial that they’re guaranteed to get the treatment that’s being researched, versus taking the chance of even getting the standard of care. And so that’s another kind of important thing, is that you don’t have to do a trial that’s randomized. You can look explicitly for trials that are going to guarantee that you get the treatment that they’re doing the research on.

Speaker 1 43:47
And there’s also crossover, that you can do, some trials have crossover.

Adrian Terek 43:07
Exactly. Yeah. So if it turns out that you know that the standard of care is not working for you, what have you, then you can crossover. Or if it turns out that the other treatment is showing benefit, they’ll allow you to just hop into the other group. So there’s really not a lot of reasons that patients shouldn’t really look carefully at clinical trials, because it does give them the opportunity to access some very promising treatments, especially when the standard of care is not very promising. There’s lots of opportunities and even other groups that help with things like travel expenses. So there’s a lot of people working in this space to try and make it as easy as possible for patients to participate in trials, because it does help everybody. It often helps the patients. There’s numerous studies that show that patients who enter clinical trials actually have better outcomes than those who don’t. It helps society at large, because we learn more faster so we can come up with more optimized treatments and get those to patients faster. So it’s in a lot of people’s interest for clinical trial participation to increase. And like I said, there’s a lot of great groups that are doing a lot of work in trying to break down some of these barriers.

Manju George 44:18
I wanted to touch on one thing. So Adrian, what you’re really saying is that if you’re a Stage IV patient, and you’re anyway getting standard of care, like, for example, in CRC, you’re going to get either FOLFOX or FOLFIRI or FOLFOXIRI, you’re saying that if a trial is testing an experimental drug, and it has an arm where any of these would be the other medication, so then getting on a trial just makes a lot of sense, right? Either you will get the therapy that you will anyway, get at your local clinic, or you will get an experimental treatment, which may be very likely to be better than the standard of care, right?

Adrian Terek 44:56
Well, I wouldn’t go as far as saying very likely, but especially once you get to the point where they’re starting to randomize, it means that the data so far in the previous trials really are suggesting that this new experimental treatment is quite beneficial. So like you hit the nail on the head, at worst, they get the exact same treatment that they would get at their local clinic. So they’re not losing anything in that regard. And often what happens is they actually get that same treatment, even in the experimental arm, the new treatment is in addition to that. So they get, like you said, FOLFOX or FOLFIRI or what have you, plus this new treatment. So they’re getting either the standard of care or the standard of care plus plus. And so again, there’s a lot of possibilities that that plus plus can prove to be beneficial. And so patients shouldn’t worry about losing out by being in a trial. I think that the the bigger worry, once patients understand how beneficial trials can be, is they should worry about losing out on getting in the trial. That’s where they need to start putting their focus on, is accessing clinical trials as efficiently and effectively as possible, because they will often give them a better outcome. And for some patients, that outcome is that home run. That’s the other key, right? I can’t stress enough that yes, it’s not the case for the vast majority of patients, but there are always some people, and this is where hope comes in, there’s always some people in these trials, where you look at the data and you’re like, holy crap, this person’s alive for the last 10 years, and statistically, everyone was gone after a year or a year and a half. And so believing, not blindly believing, but at least having hope that there’s a chance that you can be that person, I think can really give people a lot of purpose when it comes to that kind of stuff.

Manju George 46:48
When is the best time to look for trials?

Adrian Terek 46:50
Yeah, I want to jump in on that because I think that’s really key. You mentioned, Julie, about myths with clinical trials, and a lot of patients say, I’m going to be a guinea pig or clinical trials are a last resort. The guinea pig thing is very often not true, right? If there is no reason to believe that this treatment will be helpful, then there’s also no reason that a patient should really want to do that trial over other ones where they do have some data. So the reality is that not many patients in clinical trials are true guinea pigs, where they’re being given a treatment that no other human being has had before. The vast majority of treatments are treatments that have already undergone previous clinical testing. They’ve been tested in other different groups of cancers, and now they’re just testing it in a new kind of cancer. So there’s almost always quite a bit known about these treatments, and specifically, they look heavily at the adverse events. So by the time a trial can be”recommended to you as promising,” there’s a lot of information that already exists on the potentials for benefit and the risks that are involved. So the guinea pig thing is truly a myth. There’s very few patients who are really getting a treatment that has only been given to one other human being before, and nobody really knows what’s going to happen. The other thing is when to look at trials. If anything, my story is about looking as soon as possible, but simply put, at any point in your cancer treatment, there is probably a clinical trial that offers the potential for benefit. And so even if you’re Stage I and your doctor’s recommending some surgery, I guarantee, there’s a trial out there that is testing that exact same surgery your doctor is recommending, plus the addition of this one other treatment that has shown some benefit, and they want to see if adding it to surgery helps. And when it comes to cancer,it really is a game of rolling the dice, right? Every time you do a treatment, the hope is that it shrinks the cancer and helps you live longer, and most patients are not going to roll those dice 40 times, right? You’re gonna sort of do the treatments until that treatment stops working. You then have to pick the next treatmen and hope that one works. If it doesn’t work, you pick the third treatment. And along the way, unfortunately, if these treatments aren’t working, then your cancer is getting worse, and so at some point you do become potentially too sick for more treatment, or too sick to participate in trials. So when a trial can offer you the ability to potentially benefit from these new treatments, and you only get to roll those dice when it comes to doing treatments a few times, then you really want to maximize that utility by looking at trials at every stage of your treatment, because every time you roll those dice, if you can increase the odds in your favor, then the chances of you having a better outcome are also better.

Manju George 49:52
What do you recommend for people to become familiar when they start their search for trials?

Adrian Terek 50:00
You know, this is not easy, right? People shouldn’t expect to be able to become good at this in an hour, right? But when your life is on the line, you should probably be willing to put a little bit of extra effort in but there are, of course, other fantastic resources, obviously Colontown. I’m not even directly involved in colon cancer at the moment. It will be a part of Life Trials in the future, but I became part of accessing and talking to people in Colontown because of how impressed I was with what you guys have built. I mean, the the expertise in the community is unparalleled, and so I do always recommend that all patients find a disease specific community, because they’re going to be able to learn from the experiences of other people who are further along in the journey. And there’s often going to be people like both of you, who are exceptional advocates, who really have a high level of knowledge and are really willing to help people, even on an individual question by question basis. So patient centric support groups and communities like Colontown, they really make all the difference.

Julie Clauer 51:17
One thing I would just add to that too, is to think about your network broadly. Because everyone tells you, what can I do to help? What can I do for you? And usually it’s like, I don’t know. I don’t need any more meals, like, I don’t know what to tell you. And when I was going through the process, it does take a lot of effort. It does take a lot of time, and it takes a certain kind of mindset for it. And I have a friend who is in finance. She’s not even a science person. She’s not a cancer person, nothing. But she loves spreadsheets like nobody’s business. And so I had her help me just organizing information and kind of outlining and gathering and putting in inputs and things like that. And it was so very helpful. So I think the key is, if you don’t have to think like, oh my brain, it’s too overwhelming for me. Yes,it will be, but it doesn’t mean that it has to be. I think there’s people in Colontown. There’s also people totally unrelated to what we’re doing that can help because also, she didn’t have any biases about any of the information. She just was really doing it as, like, from a research kind of perspective, from her job. So just throwing that out there.

Adrian Terek 52:29
Perfect.

Julie Clauer 52:32
There’s other ways to think about getting help on it and not being totally overwhelmed, because you know. whenever I need there’s something sciencey, I don’t understand it, I call Manju and so that’s the power of having and knowing different people and pulling them in where it makes sense.

Manju George 52:52
Yeah, I had a comment there. Some of the decisions, yes, there is a lot of science and finding out what works and all of that, but there is a lot of decision making in the whole process, which is unrelated to any of it. Sometimes, you see these two things and you’re really not sure what to do. So if you have a good friend and they can ask you some questions andkind of get things clearer in your mind, even if they don’t understand any of it, you might be able to get to the answer pretty quickly, or you might know what you don’t want to do, right? That is also useful. So it’s important to get many different viewpoints, and different people who you can talk to. And it doesn’t have to be all sciencey and all clinical trials related, but the important thing is to start doing it early on. As you get diagnosed, talk to your family or friends and find out, what is it that you want? What are your goals for treatment? What are your short term goals? What are your long term goals? And how are you going to get there and having that thought in your head, and then you’ll be able to fit clinical trials or standard of care treatments, or whatever else, properly, because you have that framework in your mind. And that’s really important.

Adrian Terek 54:00
Exactly, I mean, perfect examples there. One of the people I’m very grateful for from my mother’s journey, as I was first kind of diving into this is my closest friend happens to be a statistician, so when it comes to understanding and numbers and these sort of things, he was very, very useful in teaching me so I could, then again, become my own advocate for my mother. And I think most people, if they look around, will see that they have people in their life who might be a little better than they are at certain things, and can help them kind of assimilate some of this stuff. But the other key thing, and I think, reason that starting early is so important, is because, it is a lot to take in and to prevent overwhelm, doing it slowly over time can actually be the better approach, right? What’s that old saying? How do you eat an elephant? One bite at a time? Right? You don’t try and swallow the whole elephant at once. That inherently leads to being overwhelmed. But if you immediately jump into this and start to chip away at it just a little bit every day, people will be amazed how much they learn over time. And we see this all the time in Colontown, right? You watch this journey of patients who they show up and they’ve just been diagnosed, and it’s all really emotionally getting to them, and they’re having difficulty understanding all the information. And then you see them a year later, and they’re holding hands for the next group of people who have just joined Colontown because they’re, like, been there, done that. Here’s what you need to know, here’s what works, here’s what doesn’t, here’s this. And they’ve now become experts. But it takes time to get there, and so the sooner you start, the better off you’re going to be.

Manju George 55:46
Thank you again for your time, right? I think we have exhausted all our questions, and then maybe we’ll have another session about, you know, the specific things, like overall response rate, RECIST criteria and all of that.

Speaker 1 55:59
Yeah, how they study treatments. I’m more than happy to talk about that stuff, too.

Manju George 56:04
Thank you so much. Thank you, Julie. And this was great.

Julie Clauer 56:08
Thank you. It was.

Adrian Terek 56:09
It has been an absolute pleasure. I appreciate the invitation.