Treatment Talk | Clinical Trials as Treatment for Muscle Invasive Bladder Cancer (MIBC)

January 8, 2024

Clinical trials are an essential part of cancer research. They may provide possible treatment alternatives to patients who have not had success with standard and approved therapies for muscle invasive bladder cancer (MIBC) as a radical cystectomy. Your doctor can help you determine such if you might be a candidate for a clinical trial. Dr. Karine Tawagi and BCAN patient advocates share what should you know about this treatment option and what has been the experience of other patients who have taken the clinical trial treatment path.

With Dr. Karine Tawagi

Year: 2023

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Introduction to Clinical Trials for Muscle Invasive Bladder Cancer

Transcript (PDF)

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Q&A on Clinical Trials for Muscle Invasive Bladder

Transcript (PDF)

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Full Transcript for Treatment Talk | Clinical Trials as Treatment for Muscle Invasive Bladder Cancer (MIBC)

Stephanie Chisolm:

Hello, and welcome to Treatment Talk, What You Need to Know About Clinical Trials As An Option To Treat Muscle Invasive Bladder Cancer. My name is Stephanie Chisolm, and I’m the director of Education and Advocacy here at the Bladder Cancer Advocacy Network. I want to remind everyone that as a participant, you’re here in listen only mode. If you have any questions, please be sure you drop that question in the Q&A box at the bottom of your screen. And we will save all the questions for the end of the program and should be able to get through everything today. So ideally, when we join these programs, we have these Treatment Talks, for instance, this Treatment Talk about what you need to know about clinical trials as an option to treat muscle invasive bladder cancer, we have some general objectives. What we really want to do is help increase understanding of existing and new treatments, and in this case, clinical trials for the whole spectrum of bladder cancer diagnosis.

They’re not just for advanced disease. And then showcase patient questions that you can ask to help empower you to be a good communicator with your healthcare team. And we highlight some current treatment advances for bladder cancer, keeping in mind, of course ,that there are no new advances that are going to be approved by the Food and Drug Administration without clinical trials. I’d like to start just by thanking the sponsors of the treatment talks, the EMD Serono-Pfizer partnership, Merck, UroGen Pharma, and Bristol Meyers Squibb for their support. Today’s program, What You Need To Know About Clinical Trials As An Option To Treat Muscle Invasive Bladder Cancer, features Urologist Dr. Karine Tawagi from the University of Illinois College of Medicine, where she’s an assistant professor. Dr. Tawagi has joined the BCAN patient advocates, excuse me, joined by be BCAN patient advocates, Alan Soles and Karl Pritchard, who both have participated in clinical trials. Hi Alan, and hi Karl. It’s good to see you on here.

Patient Advocate Alan Soles:

Hi, Stephanie. Good to be here.

Stephanie Chisolm:

And Dr. Tawagi, thank you so much. You’ve got a great presentation. You’re a urologist treating mostly non-muscle invasive and muscle invasive disease. What is the standard of care for patients with muscle invasive bladder cancer?

Dr. Karine Tawagi:

Sure. So I’m going to just share my slides here. Let me just pull this into PowerPoint mode. And just a quick correction, I’m actually a medical oncologist, but we work very closely with urologists. So I’ll refer to where we as medical oncologist fit into the spectrum of treatment for muscle invasive bladder cancer. And so just an overview of how bladder cancer is diagnosed. So you may have blood in the urine or pelvic pain or burning upon urination, among other symptoms, that may prompt further investigations, including urine tests and blood work that may eventually lead you to a urologist. And the urologist, in order to diagnose bladder cancer, will put in a camera, also known as a cystoscope, you can see on the left hand side, into the bladder in order to visualize if there is indeed a tumor. So you can see, on the right hand side here, what a tumor may look like.

And then in terms of one urologist refers on to medical oncologists such as myself, these settings where we will see patients with bladder cancer are if they have what is considered to be high risk bladder cancer, also known as muscle invasive bladder cancer, or if they have cancer that has spread outside of the bladder, whether it’s to lymph nodes or other organs. In terms of lymph nodes, those are part of the immune system, and they are these bean shaped organs. There are hundreds throughout the body. And often if a cancer spreads, that is one of the first places it spreads to. And I’ll go over a little bit more terminology of what muscle invasive bladder cancer is. And so in order to determine if the cancer is muscle invasive, think of the bladder as having three layers, with the middle layer being the muscle.

So you want to find out how deep does the cancer go from the bladder into these layers of the bladder wall. And so the way that we find this out is through something called the transurethral resection of the bladder tumor, also known as a TURBT, which is something that the urologist will perform. So essentially, they will scrape off this tumor, and then they will find out how deep it goes. And the way that they can find out how deep it goes is by having a pathologist that gets the slides from the biopsy under a microscope and looks to see how deep this tumor may go. And so in terms of the stage of a bladder cancer, again, as you can see on the right hand, upper side here, this is what a bladder looks like, with the middle layer being that muscle layer as I mentioned. And we want to find out how deep does the tumor go.

So when you’re looking with the camera into the bladder, you often can’t tell how deep it actually goes, but these ones that are most high risk are the ones that invade into that middle muscle layer or beyond. And so in terms of how far these tumors go, sometimes we can’t fully tell just by this camera and resection procedure alone. And so until the bladder is fully removed, sometimes we’re not able to tell how deep does the tumor go. And so other ways that we can help determine how high risk a bladder cancer is by doing what is called a CT scan, or computed tomography scan. And on the left hand side here, you can see what a normal bladder looks like. So this big gray, almost square thing is a normal bladder. And then on the right hand side here, you can see what a bladder cancer may look like on a CT scan. So we can see here that there is a mass within the bladder.

And then we also do CT scans to determine if the cancer has spread outside of the bladder. And so in this case, you can see by the arrow here, that the bladder cancer, when they did the CT scan, appeared to have spread to a lymph node. And so this is important in terms of knowing what the treatment options may be. And so this talk is focusing mostly on muscle invasive bladder cancer, or these high risk bladder cancers that are located within the bladder but may not have spread. And in terms of the result, if you remove the bladder, half of the bladder cancers invade to the muscle of, which 80% of patients survive long-term, a quarter of these bladder cancers both through the muscle to that third outside layer, and of those, 50% of patients survive long-term, but then a quarter of patients actually have bladder cancer that has spread to the lymph nodes, and 30% of those survive long term.

And so one of the problems is that we can’t always reliably tell how deep the cancer goes, as I mentioned, but half of these patients will have the cancer come back at some point. And this is why patients are referred to medical oncologists such as myself in order to discuss treatments to reduce the chance of the cancer coming back. And so why do we use drug treatment and bladder cancer? So as we mentioned, we can remove the bladder by surgery, or we can also do radiation in order to eradicate the cancer in the bladder itself locally. However, cancer can spread both through lymph nodes or the lymphatic system, as well as through blood vessels. And so drug treatments can target cancer anywhere in the body, including cancer cells that you may not see to the naked eye on both CT scans or with that cystoscopy camera procedure. And so when do we add drug treatment? And this is what medical oncologists will manage. So we like to add drug treatment before surgery or radiation for those that are high risk.

And as we talked about, the high risk bladder cancers are the ones that invade into that muscle layer or beyond. There can also be consideration of drug treatment during radiation if a patient decides to have radiation instead of surgery, and then after surgery, for those that are high risk, there is also consideration of more drug treatments. And then for the patients in which the bladder cancer comes back, it’s there’s also many options for drug treatments. And so this is really a chemo approach in terms of how bladder cancer is managed. So there is chemotherapy which is managed by medical oncologists such as myself, and it can either be given before surgery, which is called neoadjuvant or after surgery, which is called adjuvants. There can be consideration of surgery to remove the bladder, and that procedure is called the cystectomy. And then there can also be a bladder sparing approach for select patients if they meet certain criteria, in which case they don’t actually have their bladder removed.

They just have that scraping procedure where the bladder tumor within the bladder is removed, but they actually keep their bladder and get radiation to the bladder, along with chemotherapy. And so what is the standard of care chemotherapy for patients with muscle invasive bladder cancer? The most commonly used chemotherapy in this setting is something called cisplatin, and it can be given before or after surgery, usually in combination with another chemotherapy called gemcitabine. But one of the issues with this chemotherapy cisplatin is that there are many patients that cannot receive cisplatin for various reasons, including if they have many other medical problems, if their kidney function is decreased, if they have significant hearing problems, if they have significant neuropathy, which is numbness and tingling in the hands or feet, for example, some patients have this from diabetes, or if they have significant heart problems.

And then there are also other chemotherapies that can be given for patients that can undergo the bladder sparing approach, in which case they don’t have surgery to remove the bladder. And so those patients get chemotherapy with radiation. And the names of those chemotherapies are called gemcitabine, 5FU with mitomycin C, and then cisplatin, which is the same chemotherapy I talked about in the previous slide. And then for those that have surgery, in the last few years, there was also the approval of immunotherapy, which can be given for one year after surgery. And this is called Nivolumab or Opdivo. And this has been kind of a new era of treatment in bladder cancer.

And so I wanted to just quickly mention, how does immunotherapy work? So we know we’ve had chemotherapy for decades and it’s been used in many different cancer types, but immunotherapy has been a new treatment that has come out in the last decade or so. And basically, immunotherapy uses your own immune system to fight off cancer cells. So your immune system is a collection of organs, special cells, and it recognizes cells that belong in the body. So cells on the left hand side, and then it also recognizes cells or substances that don’t belong in the body, and it fights those things off. So that could be an infection, for example. So if you have a viral infection or a bacterial infection, your immune system will recognize that those don’t belong. It will fight it off in order to clear the infection. The problem with cancer is that it’s smart.

And so looking at this next slide, if you think of cancer as wearing a cloak in your body and floating around, your immune system doesn’t see the cancer cells because the cancer cells are smart and are hiding from the immune system. And so one of the ways that we call this cloak signal is when this cancer cell has this receptor called PDL1 that binds to immune cells called T-Cell. And so the way that cancer can function in the body and grow is because your immune system doesn’t see it. And so one of the ways that immunotherapy works is that it basically will decloak the cancer cell, and so your immune system can then see the cancer cells and fight them off. So here, you can see that the cancer cell is decloaked. So now your immune system or these T-cells can see the cancer cells and fight them off.

And these are the people that discovered immunotherapy, Dr. Allison and Dr. Honjo. And so they won the noble prize a few years ago for their discovery of immunotherapy. And immunotherapy is very successful in other types of cancer, including melanoma. So this is a patient with stage four melanoma, and you can see on the left hand side here. This is a PET scan, so the arrows here demonstrate melanoma tumors in the body, these black circles. And then the patient got immunotherapy. And four months later, you can see that all of those aero spots that demonstrate these melanoma tumors have virtually disappeared. And so how is immunotherapy being used in bladder cancer? So right now, there are clinical trials open to look at if immunotherapy would make a difference before surgery. There are also trials looking at immunotherapy, looking in combination with chemotherapy with radiation for patients that decide not to have surgery to remove their bladder.

And then after surgery, as I mentioned, there already is an approval for immunotherapy with this drug called nivolumab. And this was approved based on clinical trials that were done in the last few years. In terms of cancer that has spread outside of the bladder, we’re looking at immunotherapy in the first line setting as the first treatment for someone with stage four bladder cancer, and it is already approved for patients in the second line setting. So there definitely is immunotherapy in bladder cancer. However, we’re trying to see if we can get it approved in more places to see if we can have better responses.

And so what is new and drug treatment in muscle invasive bladder cancer? So we know that we have radiation, which is an option for some patients. We have surgery for some patients, we have chemotherapy. And then now, as I mentioned, we have immunotherapy, and also something called targeted therapy, which is being studied in this space. And chemotherapy can be very effective. So this is showing that, in a certain type of bladder cancer, chemotherapy reduce the chance of the cancer coming back after surgery by 51%. So we know that chemotherapy works. That is why it is the current standard of care in muscle invasive bladder cancer. But we are getting a better and better understanding of how cancer grows. And so these are just different pathways by which cancer grows. So cancer doesn’t just grow usually by just one mechanism. There are many different ways that cancer can grow.

And so we’re figuring out how in this cycle of cancer growth can we target the cancer in order to have even better responses than what we already have. And so I mentioned already immunotherapy as one of the ways that is being studied, but there are other mechanisms, such as fibroblast growth factor, which is also known as FGFR, which some patients have that have bladder cancer. And then there is also Nectin-4, which is basically like a little antenna on bladder cancer cells, and that is also being targeted as a new form of bladder cancer treatment. And so why clinical research? So only 5% of patients participate in clinical trials, but really, it’s the only way to continue to advance cancer treatment. And so if we have standard of care options, as I already showed you, why might a patient want to do a clinical trial? So some of the pros is that you can get access to the newest, most exciting treatments. You can have close monitoring the study because you’ll have an extra contact within the cancer center in terms of research associates. That can be a great resource.

Some of the cons is that there may be a higher time commitment and extra testing. That the new treatments can have unexpected side effects. And having a trial doesn’t assure that the new treatment will necessarily work, but it is being compared to the standard of care. And so what are current bladder cancer trials? So I showed you all of the different ways that bladder cancer can grow. So there are different drugs that are being studied in all of these areas to see if we can improve the outcomes. So that FGFR mutation that I talked about, so think about that also as an antenna that is on some bladder cancer cells. There are drugs that specifically target that antenna called Rogaratinib and Erdafitinib. There are also drugs such as Ramucirumab that are being studied. And then there are many types of immunotherapy that are also being studied, in addition to the Nivolumab, or Updivo that I mentioned. And some of those include one that is also very common called Pembrolizumab or Keytruda.

And then that other antenna on bladder cancer cells called nectin-4, there is a drug called Enfortumab Vedotin, which is being studied in this space as well. And so in terms of clinical trials in muscle invasive bladder cancer or this high risk bladder cancer that has a high chance of coming back, we have many clinical trials looking at immunotherapy with standard chemotherapy, or with some of these newer drugs. So these are just some of the names of the clinical trials that are ongoing right now and some of them are for patients that can get that cisplatin chemotherapy. And then as I mentioned, there are many patients that cannot get the cisplatin chemotherapy and there are other trials looking at these new treatments in those patients. And that is how we’ll be able to have more options, is by having these clinical trials show us the results and change what the current standard of care is.

And so what is some advice for patients? So bring an extra set of ears, write things down, make sure that your voice is heard. It is a complicated decision for this muscle invasive high-risk bladder cancer. So oftentimes, the entire team will discuss the case and that includes the surgeons, the urologist, the radiation oncologist, the medical oncologist, such as myself, the pathologist that look at the slides under the microscope, the radiologist, the ones that read the CT scans. Make sure you ask for handouts in case you need to think about your decisions. Ask for alternatives and consider clinical trials. And so what questions should other patients ask about clinical trials if they’re interested? So they can ask questions like, what is the purpose of the trial? Why do researchers believe that the treatment being studied may be better than the one being used now? Why may it not be better? How long will you be on the trial? What kind of tests and treatments are involved?

How will the doctor know if the treatment is working? How will you be told about the trial’s results? How long do you have to make up your mind about joining the trial? Who can you speak to about questions you have during and after the trial? Karl and Alan shortly. Also, we can ask about possible side effects to the standard treatments, and then also questions about daily life. So how often will you have to come to the hospital at the clinic? Will there be any part of the trial that requires you to stay in the hospital? If so, how often and for how long? And then how often will you have checkups after the trial? So in summary, bladder cancer treatment is changing. Right now, chemotherapy is a really important part of treatment to reduce the risk of the cancer coming back, given either before surgery with radiation, or after surgery.

We have immunotherapies that are already adopted for stage four metastatic bladder cancer, and right now, it’s being tested in about every aspect of this high risk muscle invasive bladder cancer in order to see if it should be added to chemotherapy or instead of chemotherapy. So it is important to consider participating in clinical trials and communicate with your whole team about the best options for your situation. And thank you. Any questions?

Stephanie Chisolm:

That was wonderful Dr. Tawagi. So can you just tell us what got you excited and motivated to be involved in clinical research? There are plenty of urologists and medical oncologists studying bladder cancer out there. What triggers them to be researchers like you are?

Dr. Karine Tawagi:

So I think when you look at the number of patients with muscle invasive bladder cancer that have the cancer comeback, about 50% if you average everyone, and we want to really reduce that number. So if we can get those outcomes to be even better for our patients, the only way that we can really do that is by studying new drug treatments that can hopefully improve those percentages and odds for our patients, that they can live longer without their cancer coming back.

Stephanie Chisolm:

Okay, great. So if you want to stop screen sharing right now, we’ll open it up to questions. I would really like to bring in Alan and Karl who have been involved in clinical trials. Alan, you volunteered for a clinical trial. What motivated you to consider going into a clinical trial instead of just accepting the standard of care?

Patient Advocate Alan Soles:

Well, it was an easy decision because my standard of care, at that point in time, I wasn’t getting any treatment. And so I approached my oncologist and said I’d be interested in any kind of studies that are available, because the only way that I got any treatment is from other people doing studies beforehand to see if they worked. So I was more than willing to be on board to be a participant.

Stephanie Chisolm:

Right. So tell me a little bit about your diagnosis, if you don’t mind sharing.

Patient Advocate Alan Soles:

Yeah, I was diagnosed back in September of ’19. And I had my scope and my cancer was at top of my bladder and was too large to be resected. And so I had my bladder removed in April of 2020. And I was diagnosed at that point in time with metastatic bladder cancer. It spread to lymph nodes and I had spots on my lungs. And so we were just monitoring at that time. And that’s why when I approached my oncologist and said, “Hey, if there’s a treatment, research, I’d be more than happy being on it.” And he found the Keytruda one, and so I started with that one.

Stephanie Chisolm:

So obviously Dr. Tawagi, you see a lot of patients that would be good candidates for clinical trials. How do you bring it up to a patient, because it is taking a little bit of a risk to the, stepping off into the great unknown of science? But how do you suggest this to patients?

Dr. Karine Tawagi:

So the way that we approach trials, most trials in this setting will be at least the standard of care with the possibility of something better than the standard of care. So that’s kind of how I approach it. Sometimes there are treatments for example, where you might get standard of care and you either get a placebo or an addition of a new treatment, but you’re at the very least getting standard of care. So we’re helping to advance what the current treatment regimens are. So I think really for any patient that’s willing to do a clinical trials, they have the possibility of a new treatment that could be even better than what we already know works. And so if a patient is eligible and we have it at our center, I certainly encourage it. And again, it’s always a choice never. It’s never forced upon anyone.

And it’s definitely a risk benefit discussion of all of the aspects that we talked about. What can be expected side effects, does it work for their schedule to come in more frequently? Perhaps some patients may need extra tests in order to enroll in the clinical trial, including additional CT scans or additional biopsies, depending on the trial. So definitely want to consider all of those aspects as well.

Stephanie Chisolm:

Sure. And you brought up a really good point when you said you’re either going to get standard of care plus the new treatment or a placebo for that, but you’re still going to get standard of care. You’re going to get the regular care that you would get as treatment anyway. I think that’s important because a lot of people might be a little bit gun shy about going in a clinical trial because they’re afraid of being given a pink sugar pill, and they think they’re not going to get treated initially because they’re going into a clinical trial. But that’s not the case, correct?

Dr. Karine Tawagi:

Correct. In this setting, we’re giving at least what is considered the standard of care, because ethically, it wouldn’t be right to give someone something that’s below the standard of care. Sometimes there are trials where you’re comparing the standard of care versus something that has the promise of being even better than the standard of care. So there are a lot of trials like that right now.

Stephanie Chisolm:

Yeah. Okay, good. And Karl, you got involved in a clinical trial, so let’s get you to unmute your microphone. There we go. So tell us a little bit about your experience, your journey, and then why you got involved in a clinical trial.

Patient Advocate Karl Pritchard:

Well, I won’t go into a lot of detail. It was early 2014 that I was diagnosed and I had my surgery. My tumor had already metastasized, spread throughout the body, so simple treatment wasn’t going to work too well. My kidney, my left kidney was… Well, where the tumor was blocked off my left ureter, so my left kidney was severely compromised. So they said I could not have chemotherapy because of that. So they took me right into surgery and removed my bladder. And when I came out of surgery, the doctor told me that the gold standard of care is chemotherapy. He said, “But you can’t have it because of your damaged kidney.” And he said, “Go home and get your affairs in order. You have about three to six months.” And now when I had first gotten my cancer diagnosis, I’d gone on the internet and gone right to the BCAN site, found it very quickly, did tremendous research and learned an awful lot about immunotherapy.

And I asked the oncologist at the hospital about immunotherapy, and he said he’d never heard of it. Evidently, it was fairly new in 2014. I don’t know. So I went home, I talked to the lawyer, I got everything all straightened out, but I had to see the local oncology center. They were going to track me and track the progression of my cancer. I asked the doctor there about immunotherapy and the doctor said, well, just by coincidence, we’ve just started participating in a trial for an immunotherapy drug, and I’ll check and see if it’s still open. And she came back and told me about it a day later, “Congratulations, you’re in the trial. You’re the last person worldwide that’s been selected. They were closing it down. You’re the last one to get in.” This trial was for a drug called Atezolizumab, or the brand name was Tecentriq.

I got there… I was in… What do they call it? A stage one trial, I think, the one where there is no control group, no placebo. Everybody got the drug. For me, the drug was tremendously successful. As a matter of fact, the head of the oncology center in Virginia calls me his poster child for immunotherapy. He said he’s never seen successful progression go that way. However, a problem with the Atezolizumab, if I’m saying that right, Tecentriq, was that it taught the immune system how to detect and attack cancer cells very well, but it unfortunately also taught the immune system how to attack some good cells, and it turned around and started attacking my kidneys. But the cancer, all trace of cancer was gone within six months.

So when they stopped the clinical trial, which was after six months, I was okay. I didn’t have any more cancer. I did have a decreased kidney function, but I’m still fine. I attribute the fact that I’m still vertical today to that cancer trial, to that clinical trial. Because at the time, based on what I’d been told, I had no alternative. And it really worked for me. It really worked.

Stephanie Chisolm:

So what would you both suggest to a patient who’s considering a clinical trial, but is like, I don’t know if I want to do this or not. What would be your advice? What would be some questions? In addition to the wonderful questions that Dr. Tawagi had listed, what would be some other tips that you might give to them in terms of making sure that the clinical trial is the right choice for them? Do you have any ideas, Karl or Alan?

Patient Advocate Karl Pritchard:

Well, I do. I would say, first of all, because I’ve done this for people, if you’re in a clinical trial, the sponsor of the trial is very, very concerned about how it’s working in everybody. So if you’re in a clinical trial, you’re going to be heavily supervised. While I was getting my infusions and my immunology drug in a large infusion room at the drug oncology center, there were dozens of people getting chemotherapy. They came in once every three weeks and got chemotherapy. They saw the doctor once every several months. I saw the doctor every three weeks. Every three weeks, I had my immunology infusion and I saw a doctor for a comprehensive scan every three weeks. I think that’s something to say to them. You’re going to get more attention, I think, in a clinical trial. Plus, you might be opening the door to something that’s really better than the alternative.

Stephanie Chisolm:

Alan, how is that for you as far as your care with the clinical trial? Just take it off from mute.

Patient Advocate Alan Soles:

Here we go now.

Stephanie Chisolm:

Now, we can hear you.

Patient Advocate Alan Soles:

Yeah. No, I had the same experience as Karl had, and the sense of the amount of care and things that I was followed with, it was fantastic. And in terms of questions to ask and stuff like that, I think Dr. Tawagi is right on board. Everything that she has listed is exactly what I asked when I went in. I would copy off that list and I would take it with me into another study, I would take that list with me and use that as a base plate.

Stephanie Chisolm:

Right. And we will make that list available when we put the transcript up on the website. So that whole list will be available. You can print out a copy and bring it with you if you’re watching this as part of the recording, so absolutely. So Dr. Tawagi, when you’re considering patients for a clinical trial, there are inclusion criteria, which means they have to have a certain aspect of the disease and there are exclusion criteria. When somebody doesn’t qualify for a clinical trial because they have an exclusion criteria, how do you break that to them, especially when they were really excited about being in the clinical trial?

Dr. Karine Tawagi:

Yeah, that’s difficult at times because it is the promise of a new better treatment. But of course, we want to be able to give these things safely. So for example, immunotherapy, which Alan and Karl were both on, if you have a significant history of an autoimmune disease, you might not be able to get immunotherapy because the risk of your autoimmune disease flaring up would be significant. So we really have to weigh kind of the risks and benefits, and we’re always thinking of new trials that can help perhaps include patients that were traditionally excluded. So I think the needle is moving to have wider inclusion criteria. But yes, we certainly sometimes have to break the news that someone doesn’t qualify for a clinical trial, or perhaps their disease is not the stage that we thought it was initially.

Let’s say we thought it was stage three, and now it looks like it’s stage four, then they might not qualify for a trial for those reasons as well. But it’s not that they can never qualify for a trial in the future. Sometimes, let’s say someone is stage four instead of three. Perhaps if the first treatment doesn’t work, there might be a clinical trial after that. So it doesn’t really necessarily close all the doors. There’s always options for future clinical trials as well.

Stephanie Chisolm:

Right. So when they look at all these inclusion and exclusionary criteria, one of the things I think people don’t understand is those exclusionary criteria are built into a trial to really make sure that they’re able to assess the impact of this treatment that’s not been confounded or confused by somebody’s other, perhaps comorbidity or other health concern. So that’s partly why it makes it so challenging. In general, bladder cancer tends to occur more frequently as people get older. Is there an age limit to being in a clinical trial?

Dr. Karine Tawagi:

No, there is not an age cutoff. One of the limiting things sometimes is something called performance status. So for most clinical trials, somebody needs to be able to do their daily living activities, like go to the bathroom on their own, be able to walk around. If they’re more bedbound, for example, for either from their cancer or for other medical reasons, it’s difficult for them to really benefit from the treatment. So often in those cases, we wouldn’t necessarily be able to offer a clinical trial. And then other medical issues such as significant kidney issues may preclude you from certain types of clinical trials and things like that.

Stephanie Chisolm:

Right. And that would be because your body can’t process sometimes some of the drug treatments that you might be given-

Dr. Karine Tawagi:

Right, right, right. It would be too risky and actually probably cause more harm than benefit.

Stephanie Chisolm:

Yeah. Well remember, if you’re on this webinar and you have a question, drop it into the Q&A box at the bottom of your screen. So looking at the general picture, I think the future looks pretty bright because people do participate in clinical trials. But Dr. Tawagi, have you ever been involved as an investigator on a trial that had to close because there wasn’t enough enrollment?

Dr. Karine Tawagi:

I have. I have. So some trials, if they’re smaller trials, if they’re not able to enroll enough patients or if there’s… Sometimes, trials close because of safety signals. So if let’s say there are side effects that were not expected, I haven’t been involved in those specifically, but that does happen at times. As Karl mentioned… Earlier, I did mention that oftentimes, you get the standard of care or another treatment or the addition of a treatment. But in earlier phase trial, such as what Karl was on, he was on a phase one trial, there is no control arm as he mentioned. So sometimes it’s an earlier phase because we don’t have any treatments in this phase. And so really, you’re either getting the treatment. There’s not going to be a comparator arm. So it’s also important to know, depending on the space that you’re in, there might not always be a control arms, and there might just be kind of one treatment and they’re trying to see what the best dose is, what the efficacy is or how well it will work, and what the toxicity or side effects are.

Stephanie Chisolm:

You brought up. A good point about the control arm, not the control arm, but the comparator arm. Do participants in a clinical trial get to pick, or do they always know whether they’re getting the treatment or standard of care only?

Dr. Karine Tawagi:

No, not always. So in the case of an earlier phase trial, so like phase one or phase two, so there are different phases of clinical trials. You might only have one arm, so you would definitely know what you’re getting. But in the case of, for example, a phase three trial, which are these big trials for which things get approved by the FDA, you might not necessarily know if you’re getting the new treatment or not. You might be getting the standard of care with either the placebo or the new drug, but you might be blinded, in which case you would not actually know if you’re receiving it or not. And the reason that they do that is so that there’s no bias in terms of whether it’s working or not by people knowing what they’re getting, both the doctors and the patients.

Stephanie Chisolm:

So sometimes not even the researchers know which one they’re giving. So they basically go out of their way to make sure all the treatments look exactly the same. So if it’s a pill, all the pills look the same and nobody really knows which one except on the backside for the data, so they can check and make sure that it’s really measuring is there an impact or no impact.

Dr. Karine Tawagi:

Exactly.

Stephanie Chisolm:

That’s important to know. So what if a patient decides, all right, I’m going to be in a clinical trial, and then they think, “You know what? This is way more monitoring. I don’t want to go into town and get monitored every three weeks. It’s really a hardship for me,” can they back out, or they’re stuck now?

Dr. Karine Tawagi:

Yeah, no, it’s always a choice. Both at the beginning and throughout, it’s not a forceful thing. It’s something that we offer. Because if I had the option, I would want to be on a clinical trial knowing what I know. But it’s always a choice.

Stephanie Chisolm:

If somebody were being seen in a community practice, not at a large institution that usually has an academic affiliation, like University of Illinois or something like that, and they wanted to go in a clinical trial, but there was no big medical hospital affiliated with the university near them, how do they get into a clinical trial?

Dr. Karine Tawagi:

So they can look for… On clinicaltrial.gov, you can search for clinical trials depending on the type of cancer that you have. So for bladder cancer, for example, you could search yourself on clinical trial.gov and see what the closest center is that might offer a clinical trial. I know that Karl mentioned he did his research through BCAN and kind of got familiarized with what was available. So patients can be their own advocates to try to get clinical trials. Even at community centers, it’s possible sometimes to get clinical trials. And if not, kind of looking geographically what the closest place might be that might offer a clinical trial.

Stephanie Chisolm:

Right. I just dropped the link in the chat box. If you all open that up to our clinical trials dashboard, that’s an important point. Clinicaltrials.gov is all the clinical trials that are open around the world, including some that are done recruiting, but they’re still out there. BCAN keeps only the open recruiting trials because what’s the point of telling you about a really exciting clinical trial if it’s not even open yet? So we have all the current open trials that are recruiting, and those are just the trials that are specific to bladder cancer. And you can sort by your disease diagnosis, so non-muscle invasive or muscle invasive, or advanced disease, and then you also can sort by your geographic location. So maybe you want to search for the closest trials to you, but maybe you have family or a vacation home in another state that would enable you to have another place to stay for six or so months if you had to, and you could look there. So that also kind of expands your footprint of potential clinical trials.

And especially if you’ve got family in Illinois, there are plenty of large academic hospitals that are doing clinical trials. But many times some of the routine screenings that need to be done, could they be done back in the community and just have those results shared with the large teaching hospital that might be sponsoring a trial?

Dr. Karine Tawagi:

Absolutely. So I did some of my training in New Orleans. And MD Anderson was about four hours away, so a lot of patients did clinical trials in Houston at MD Anderson, because it’s one of the largest cancer centers in the US, and we would monitor them in New Orleans, do their testing, and communicate the results with the other institution. So definitely can happen.

Stephanie Chisolm:

And occasionally, clinical trials will help provide transportation.

Dr. Karine Tawagi:

Absolutely.

Stephanie Chisolm:

Sometimes if you may have to come in for an overnight and it’s a little bit far, maybe they have a place that’s affiliated with the institution that you can do overnights and be able to stay there. So I think many clinical trials go out of their way to try to be accessible to the patient community, but only if patients ask. So it’s certainly something to think about. So if there are any other questions coming in from any of our participants, please feel free to drop them in. And while we’re doing that, if Alan and Karl, you have any closing suggestions or thoughts? What would be things you would share with a new patient who’s saying, “I don’t know if I should go on a clinical trial?” What would you tell them, Alan?

Patient Advocate Alan Soles:

I would want- They’re so hard because for me it was really easy because I don’t have a wife and kids, all those kinds of things. So it’s more of a matter, I think, of what’s going to be comfortable for your family and things.

Stephanie Chisolm:

Okay. Yeah. Karl, anything to add?

Patient Advocate Karl Pritchard:

Well, the first thing that springs to mind, of course thinking about myself, clinical trial, in my mind, gives you a better chance to survive. If you don’t go into clinical trial and you take, for example, the chemotherapy, I don’t know what the statistics are, and I’m sure the doctor does, but I know that when I started my immunotherapy, the prediction was, at that time, they had Keytruda, Opdivo, and a few others, and they said the predicted survival rates for people on immunology was higher than those that received chemotherapy, and of course, the quality of life was much higher. I would say to a person considering it, I don’t see that they’ve got anything to lose and they have everything to gain. I don’t know why anyone would turn it down, but I’m sure- I look at it as the chance to remain vertical. That’s all.

Stephanie Chisolm:

Okay. That’s a good way of looking at it. Any closing remarks, Dr. Tawagi?

Dr. Karine Tawagi:

Yeah, I think in this space of, you know, we’re talking about muscle invasive bladder cancer, so a little bit different than what Alan and Karl had because there’s had already spread. But in this muscle invasive space where the cancer really hasn’t spread and we can give chemotherapy after or remove the bladder or give chemotherapy, sorry, before or after, we know that a significant portion of those patients, the cancer comes back. So we want to reduce the number of patients for which it comes back because the outcomes will be longer, you’ll remain vertical for longer, as Karl mentioned.

And so we want to try to include more patients so those that have kidney issues that can get the standard of care cisplatin, we need more trials in order to determine if immunotherapy can be given in this setting. And really, we want to improve the treatments of bladder cancer. There has been tremendous advances in other types of cancer like melanoma, like I showed you, but bladder cancer still has a long way to go. We have made tremendous progresses in the last decade with all these new treatments, but there’s definitely a lot more that can be done, and the only way that we’re going to improve it is with clinical trials.

Stephanie Chisolm:

Excellent. Well, with that, I’m going to thank you all for a really informative webinar about clinical trials for the muscle invasive bladder cancer patient and their families, because this is a family affair in that everybody gets involved in the process. Ask questions, talk to your doctor, find out if you could do it even within your community setting. There are many community practitioners that are engaging in clinical trials as well, so don’t be afraid to ask for that. Thank you all so much for a great program, and again, I’d like to thank our industry sponsors for making the Treatment Talk programs possible. Take care, bye.

Dr. Karine Tawagi:

Take care, everyone.

Stephanie Chisolm:

Bye.

Patient Advocate Karl Pritchard:

Thank you.