Dorothy: [00:00:00] Clinical trials aren’t just for drug companies. They save lives. Bring tomorrow’s treatments to patients today and offer help and hope when options run out Dr. Elkhanany clears the miss, and there are so many about clinical trials and shows how access to those trials can change everything.
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So Doctor, [00:01:00] another big part of your time as a physician being in breast cancer, being a breast oncologist has to do with clinical trials.
Dr. Elkhanany: Correct.
Dorothy: So tell us exactly what a clinical trial is.
Dr. Elkhanany: Ooh, that’s a, that’s a great question. Well, in its core, clinical trials are, uh, ways to determine how active, uh, medicine a drug is to fight a specific disease or a specific indication. Okay, now clinical trials encompass so many different things. There are what we call phase one, phase two, phase three, and um, there is what’s called preclinical evaluation, which are things that we do. All the things that we do before a drug reaches the level [00:02:00] where it can be, uh, used uh, for a clinical disease in humans. And then you have a clinical trial. I have phase four, which is essentially after the drug is approved. So, um, all of these are clinical trials and the goal is to see how active a specific drug is.
Dorothy: Let’s step back even one more. Why do we need clinical trials?
Dr. Elkhanany: In a nutshell, every medicine that an individual is using to, for their health, has been in a clinical trial, and think of clinical trials, really think of it at that test that you have to pass as a drug in order to be out there in the pharmacy. So any medicine that you close your eyes and pick out will be, uh, have been validated in a clinical trial.
Dorothy: So, that’s a good word. It’s validated, it has proof behind it that it actually works.
Dr. Elkhanany: Correct. And to, to, to be frank, most [00:03:00] of the medicines would have some sort of activity. Uh, we never reached the clinical trial stage without having some sort of an activity. The clinical trials help to put that activity into context. How big of an activity is it? And also about side effects. How can we weigh side effects to benefit?
We have to have more benefit than side effects, otherwise it’s not worth it. And um, and, and, and this is why clinical trials when they start actually, so phase one is think it at the drug that we just started really to understand its side effects. That’s really what phase one is all about side effects. What is the best dose? Do we need that high of a dose? Should we go down a little bit? And then once we feel comfortable about the dose and people are doing fine, we go to phase two, which looks mostly at the efficacy of the drug. And a lot of the drugs that on phase two tend to show some sort of activity. Does that mean that they are [00:04:00] working?
But then comes phase three and phase three really ask a very simple question. Is it working better than what we have right now? You know? And, and that’s what phase three is. So almost always phase three trials tend to compare two things. What we’re doing right now, which by the way was yesterday’s clinical trial, right? So what are we doing right now, the, standard versus the new treatment? The new modality. And, uh, once the test passes, that point gets the seal of approval, gets out to be in the market.
Dorothy: So why is there a problem getting people to go into clinical trials?
Dr. Elkhanany: I think there is a huge misunderstanding about many of the aspects of clinical trials and, uh, and I understand what this, what this exists. Historically, unfortunately, there has been multiple situations in which clinical trials were, uh, performed [00:05:00] without certain consents and certain approvals from participants and that lived a very sore, uh, spot.
Dorothy: Talk about cellular memory, I mean. It really could go back to that in so many different ways.
Dr. Elkhanany: Yeah. And it’s not just one or two. There are, uh, a multitude unfortunately of examples through different parts of clinical trials and uh, obviously one of the famous ones was Tuskegee Ex, the Tuskegee Experiment. And, um. I get to be very familiar with it because I practiced in Alabama for, uh, three years before moving here and just really saying the word clinical trial immediately elicits negative reactions from patients again, understandably. So, however, you know, it is 50 plus actually, I would say what more, more close to almost 60 years. Now [00:06:00] and, uh, the world has changed.
And today’s gear has nothing to do with what we used to do, not just to, you know, six years, rather 20 years ago. And, and within that spectrum, there is now significant component of patient autonomy and patient understanding and patient education when it comes with what are clinical trials, what we’re hoping to achieve, what are your rights within a clinical trial.
Dorothy: So how well, how do you get past that? I mean, I’ve heard this so many times, they’re just experimenting on me. It’s just to make money for the drug companies, you know, I’m not gonna get anything out of it. So help us understand first, how do you combat that? Without education, you almost cannot. True?
Dr. Elkhanany: You cannot. You cannot. And um. And so the first thing that, that, you know, we do, first thing that [00:07:00] I do is really reach out to patients in their community so many times, uh, whenever I do any of the outreach activities, I would dedicate some time to discuss clinical trials. Why do we do clinical trials to move the needle forward?
If we continue to do the standard of care, we will not move at all. We will just do it over and over and over. So the only way to move beyond the standard is to prove that something comes in better than the standard. Now the caveat is how do we know it is better? Well, we don’t know, but we tend to try to guesstimate before we actually take it further, meaning that at every step of the way, as we’re gaining more and more in standing of these new drugs.
You know, our confidence that it is going to work gets higher and higher, and by the time a drug reach the stage, uh, of phase three, you know, uh, [00:08:00] we have a fairly good confidence that it will outperform the standard of care. But the phase three is really, is about the magnitude of, of benefit. How high are we talking about versus side effects? So, again, you know, discuss.
Dorothy: Is that, is that really measurable? I mean, if it’s a percentage better? Is that worth it?
Dr. Elkhanany: Uh, well.
Dorothy: Who makes, who makes that decision?
Dr. Elkhanany: That’s, no, that’s, that is a, a very important question. I, you know, it is not that. Now that one is, is tough to answer because who makes that decision tends to be, you know, um, ultimately might be the patient. So I can tell you. What, for example, what a medicine can do in, uh, patients who have like a bad disease, bad cancers, like a pancreatic [00:09:00] cancer, GI cancers or, or even like a bad stage four breast cancer. Uh, maybe the medicine can push the needle a couple of more month, maybe, maybe even a year with, with good quality of life. It’s worth it, you know? Um. When you talk about some cancers that tend to be very mild, indolent, you know, and they’re not as aggressive as some of the other cancers, occasionally the benefit might not be as much at the risk of side effects, but it tends to be a very, um, calculated measure. Interestingly, um, in the United States, right, we don’t significantly pay attention to cost versus perceived benefit because a lot of these drugs tend to be, uh, once the, once there is some proven benefit, the FDA would do cost [00:10:00] analysis, but the majority of drugs, um, best that preliminary cost analysis and gets approved when they have efficacy. That is not the case in Europe, for example.
Right. So they will take a medicine, they will do a very thorough cost analysis. And remember, this is a system in which everybody who’s eligible to get a drug will get the drug. There is no, there’s universal coverage, so, the, the government will be the be in the pill. So the government will sit and say, how effective is this drug versus how much money are we gonna be for it and how, how much moving the needle is it actually going to move? You actually don’t get, every drug that gets approved in the United States does not necessarily gets approved in Europe because of that reason.
Dorothy: Interesting.
Dr. Elkhanany: Yeah, so, so they.
Dorothy: ‘Cause that’s kind of backwards of what a lot of people think, oh, Europe, they just moved the drugs right on. And. No.
Dr. Elkhanany: No, none of that is not the case. There is a lot of medicines [00:11:00] that have, you know, have approval in the United States, not necessarily worldwide because of this. Um, but, um, back to to patient education. So this is really, uh, why the clinical trials are important. They move the needle forward. Now, how do the drug companies play a part in all that?
Well, it is not a secret that at the end of the day, drug companies want their medicines to work. Um, because they will get reimbursement out of it. They’ll get money back. However, in order for them to prove that they would add ton more money, you know, doing clinical trials, doing research and drug development is incredibly costly.
Um, it is estimated that drug that a, a certain drug can cost in the current day and age, somewhere between one up to $3 billion in cost and production. The clinical trials [00:12:00] are international to phase three, to in order to try a drug in thousands of patients, you will need billions of dollars for to you know, for this clinical trial to be, uh, implemented wildly and um. And this cost obviously goes into the drug, the, the, the census of the drug. All the clinical care that gets done for all the thousands of patients that typically is all billed directly to the, uh, to the drug company. All the side effects, the hospital sometimes stays that had to do with the drugs. All the teams that are being, uh, taking ca take taking care of the patient at the levels of the institution. So a typical clinical trial would be in about four or 500 phase three, four or 500 sites, uh, ac across the entire world aiming to accrue, you know, getting maybe somewhere between a thousand to almost 10,000 patients sometimes.
[00:13:00] And, um, and, um. Then to follow up patients for years and years and years to detect that signal of success. So all of these are money that adds up. So with that being said. Yeah, that is a very big decision. So if you think about it, a lot of the drug companies will not proceed with all that money, except if they have a very clear signal that that drug is working.
They call it the no, the, the go or, or no go signal. Usually towards the end of the phase two. So they see the activity in phase two, the drug is working, is working pretty good. And they say, okay, do we need to go that route or not? And um, again, in a way, um, it is true that the drug companies are the ones that sponsor the drug. You know, in, in most of these large phase three trials, but simul, but [00:14:00] in the same, uh, venue, you know, if you think about the new medicines at new products. Think of, well, it’s a simple example, but think of your tv, you know, a, each year you get better TVs. Well, they are putting the research and development into TVs.
You don’t know about that, but you know that they do. And you don’t know what kind of technology are they reaching out, you know, every year. But you know that the TV quality is getting better. The pictures getting bigger because there’s always the demand for better TVs. I know it’s a simple analogy, but if you think about it, that is the way also a lot of the drug development works. You refine the process, get a nicer drug, more active, less toxic, uh, zoom out, expand it to patients and you know, take it from there.
Dorothy: So for the patient who is in a clinical trial. They might benefit from extended life, [00:15:00] a better quality of life, like you said, if it’s not as toxic. What else would they benefit from while they’re in that trial?
Dr. Elkhanany: So.
Dorothy: These are, I mean, those are important things.
Dr. Elkhanany: These are two important things.
Dorothy: Yeah.
Dr. Elkhanany: You know, um. There is.
Dorothy: I just don’t know how you could convince someone to go through a clinical trial that may or may not work.
Dr. Elkhanany: Mm mm.
Dorothy: You know, and they’re already fighting for their life. So take me through I’m, I’m that person. What, what are you saying to me?
Dr. Elkhanany: So the conversation might change slightly about what type of clinical trials are we’re talking about. Let me explain phase one clinical trials. These are typically the ones in which the medicine might or might not work, meaning with these early phase trials. Phase one is called early phase.
We usually look for patients who might be having multiple lines of therapy already. [00:16:00] Unfortunately, stage four did this drug, that drug ran through all the typical types of care that that we know of. And then they come to me and say like, what next? What am I gonna do next? Well. We gotta think outside the box.
And when I say that, I mean we gotta see some of the medicines that are new, novel and work in a different way. And really there because the standard stuff that we’ve tried are not working anymore. So that’s your phase one and and phase one are usually given again in patients who have had all the classical treatments.
So there’s really nothing more necessarily in the realm of the classic treatments to work. Sometimes they might not work. Other times they might work, might work so well that in fact the drugs get into this, what’s called breakthrough therapy, accelerated approval, and within a matter of [00:17:00] few, maybe one or two years, it becomes the new standard of care.
A classic example with that was immunotherapy. So immunotherapy started off as this new class of drugs that no one really knew even, you know what to expect out of them. We know how they work. And by the way, one of the major contributors to immunotherapy was, you know, the immunology team at MD Anderson.
And um, and the idea was we’ll just make the immune system fight infections and you fight the immune system. That fights infection will make it fight cancer. And we’ll just, we’ll just monitor things and see how it works. And to everybody’s surprise, an incredible delight. It worked so well. That the drug went from phase ones into, you know, phase twos, got all of these breakthrough therapies across multiple times, uh, multiple cancers, and then got into accelerated approvals, which mean that the FDA said, oh my gosh, this has worked so well. We’re just gonna give you an approval out of phase [00:18:00] two until you guys have a phase three. That way we get this very active drug to patients much earlier because there was really nothing. Else out there.
Dorothy: Right.
Dr. Elkhanany: But that’s, that’s the story on phase one. We, we don’t get a lot of these drastic success stories, but we do have every now and then a really good success story that, um, that comes in. Now, another one has to do with the novel ADCs or antibody drug conjugates that are now again, uh, re revolutionizing how we give chemotherapy to patients. So antibody drug conjugates are these little tiny targeted, “uber drivers,” if you will, that have a chemotherapy in the back and then they drive to where the cancer is and they ditch the chemotherapy right then and there.
And then depending on how you design the, the driver, if you will, of that chemo. You get to drive the chemo to different parts of the body. So, um, so that’s basically.
Dorothy: Instead of all over.
Dr. Elkhanany: Exactly. So that’s different cancers, right? So re regarding where the [00:19:00] cancer is at, you know, the, the molecule carrying the chemotherapy will go right there and destroy. Again, phase one, who’s enormously successful. Tremendous success in phase one. The drug actually had activity in almost 90% of the patients.
Dorothy: Oh my goodness.
Dr. Elkhanany: And um, right, so we went to phase two, phase three. So with phase one, that that’s really the conversation. Phase two and phase three are more of the bigger trials that we know we already had a pretty good signal that is that we know that the drug works. And by works here, I mean that it will decrease the cancer, impact the cancer in some way, delay the cancer from coming back. And, um, it’s just that we don’t know how much of a benefit that will be. Is it a 1%, as you mentioned, is it gonna be a 10%, 50%? Hard to tell. So that’s why we do it, right? Always when I talk with my patient and explain to them where you are right now, the standard of care. It’s good. However, we [00:20:00] can do better. We can do a little better, and this is the educated development process of clinical trials. Here is why we think we can do better.
In my experience, once you take the time and discuss with patients what clinical trials are and what their right is on a clinical trial, including the right to say, you know, to exit the trial at any given time, this is not like a contract. Um, once they understand that. I people, people really love it. And they would say, why would anybody get, uh, standard of care? Which is like yesterday’s treatment if you have new treatments for today.
Dorothy: But there’s lots of people that don’t have a doctor that will talk with them.
Dr. Elkhanany: Well, I think that this is part of the problem, right? Um, I think that the actual process of discussing clinical trials and offering them, one, it is fairly intensive, time consuming process. And two, it also requires cultural competency as well as [00:21:00] scientific literacy about what are we offering to the patients. Um, it is not an easy task, however, it is part of, I would say, uh, what makes. What makes medicine and what makes cancer care really valuable that we can offer these drugs to our patients, and it is part of, uh, it, it should be part of our treatment.
In fact, if you look at the NCCN guidelines, which is everybody followed the guidelines, right? They will have this universal general recommendation that if you do have a clinical trial in this setting. We will prefer that to the guidelines. And we find that actually listed in every single page.
Dorothy: Really?
Dr. Elkhanany: Oh yeah. Absolutely. So, so again, but because that’s what they are trying to offer.
Dorothy: Trying to do. Right.
Dr. Elkhanany: You know, because if they didn’t say that, then somebody might say, well, why do I do a clinical trial if I have the [00:22:00] guidelines? The guidelines are yesterday’s clinical trials.
Dorothy: Oh, that’s so true. And what if that doctor decides you’re just not a good candidate for whatever reason. Uh, and makes that decision without ever talking to you. I mean, will we ever find a time when every doctor’s required to do that with, with quality grace?
Dr. Elkhanany: I wish that’s the case. So I, I think I will talk not about what used to be the case, but what I anticipate will be the case.
Dorothy: Oh, that’d be good.
Dr. Elkhanany: We are in an era in which healthcare is transforming by the day and we have now patients who ask more questions, more intelligent questions, uh, more insightful questions that pertain to their right understanding what they have and being an active participant in their disease. And I think that this is really the future direction, which is the [00:23:00] patients are now expected in a way to participate in their care. So in my practice, I, I am a very firm believer in shared decision making. I do shared decision making, which actually, you know, a lot of patients love, but some patients don’t like, some patients come and tell me, doc, don’t tell me what I, you know, what, what we think we should be doing. You tell me what you want me to do.
Dorothy: That’s true.
Dr. Elkhanany: But the majority, I would argue, the majority would want to play a part. You know, if, you know cancer takes care of cancer, takes that personal, uh, liberty and that ability to choose from you and put in that shared decision making back into the conversation helps balance this out a little bit. But going back to that point, how do you know, how do patient, how do that factor in? In clinical trials, we see many patients come now to their appointments. Who have already researched their disease and [00:24:00] even looked through some sort of apps or, um, some, you know, searched through the website about clinical trial that they might be eligible to, which I think that that is fantastic. And if they don’t, I tell them actually how to do it. I tell them, this is how you want to look for clinical trials.
Dorothy: Hmm.
Dr. Elkhanany: Um, every new patient that comes to me, um, in my clinic, I tell them two recommendations. Every single new patient, um, I tell them always try to seek a second opinion if you’re able to. Specifically for clinical trials. And I always, the second recommendation I always give them is to reach out to their insurance company to look for their oncology liaison. ’cause each insurance, you know, each person’s coverage will have like an oncology liaison that would be associated, you know, with the patient’s coverage that that’s the one that typically will help them with all the scans, the imaging and stuff like that.
These are my two comments. [00:25:00] The first one, seeking a second opinion is really mostly for clinical trials. If I’m in a place that have X amount of clinical trials, I always tell them, go get a second opinion. Also, see what clinical trials do they have and if the care is going to be similar. And this is important because when I talk to also patient in the community, and when I educate patient in the community, that becomes very, very important. Um, it’s not easy for everybody to get second opinions. But with the advent of vis, you know, of video visits and telemedicine, it certainly did improve the accessibility, you know, to an extent.
Dorothy: Oh, that’s a good point. Yeah.
Dr. Elkhanany: And there are a lot of virtual second opinions where they will review the imaging, they review the scans, and then they will comment on what patients, uh, you know, what they think from their expertise. I think that this is important in today’s age because you, it’s not just making sure that you are on the right [00:26:00] track, because again, guidelines are the same really. Most of the time the guidelines are, are what physicians follow, but it is the clinical trials and the availability of next, you know, the next phase of treatment, the next new generation, if you will, of therapy to the patients.
Dorothy: It’s not limited by your geography because of these tools that we have now.
Dr. Elkhanany: Correct.
Dorothy: Yeah. That could make a really big difference.
Dr. Elkhanany: But education is key. And understanding that, um, understanding that being in control of your own disease and being your own advocate is a key point. Now, I’m fortunate that I work in a facility at Baylor College of Medicine, which we have tremendous amounts of clinical trials. Um, we are close to MD Anderson who do have tremendous amount of clinical trials. We share patients with same patients back and forth specifically for, uh, clinical [00:27:00] trials. Um, however, there are patients in the community that do not have that privilege. Then one of the things that I have been extensively working on is how can we understand these specific limitations and is there a way to bridge them?
So when I see a patient coming in from two, three hours away. I would, for example, tell them, Hey, we have that clinical trial and let me work with the drug company and see if we can get you a voucher or, or ga uh, you know, um, um, or a gas voucher, for example or some sort of a bus voucher, at the very least. Let me see if we can get some, uh, childcare, you know, reimbursement for you. Um, and we have actually examples of certain settings, especially in the phase one in which we’re able to have lodging for patients, you know, hotel stays, um, in order to minimize that logistic, uh, uh, burden on patients.
Dorothy: And that’s so important because [00:28:00] there’s a lot of factors that could stop someone from participating that we don’t have any real control over, or the patient doesn’t. So knowing that there could be some assistance in some way could make all the difference in that decision.
Dr. Elkhanany: Right. And there are programs that are specifically designed, um, to support patients who are going to be enrolled in clinical trials, and that, that includes some of the stuff that I mentioned. But it goes all the way out to actually having, uh, some medicines supportive, medicines, supportive, uh, websites. Um, even including, uh, virtual pharmacists and virtual navigators. In fact, we have a program right now, you know, uh, uh, using virtual navigators for one of the drugs that we have, um, which the tyrosine and inhibitors that one of the pills that we use in her, her two positive breast cancer in which patients [00:29:00] can have, uh access to a virtual like pharmacist who can actually help them with their treatment and, uh, their, um, um, concerns on that pill. And so, so, and there are all these tools that, that exist out there. And it’s just the coordinating them for, for the right patients.
Dorothy: So you see a brighter future for breast cancer patients.
Dr. Elkhanany: We definitely see a brighter future. Breast cancer mortality has decreased from the 1980s until now by about 43%. And interestingly, that is a huge part of that has to do with all the advancement in the endocrine therapy, the advancement in the anti HER2 therapy. And the introduction of the immunotherapy as well as most recently, the antibody conjugates. Um, and it seems like every decade or so there is a huge revolution in the care of breast cancer in which that extends the mortality, [00:30:00] uh, reduction and the survival of patients by a considerable amount of time. Um, for example, you know, when, uh, when you look at, uh how the anti HER two therapy was developed, or tamoxifen, which is our hormone receptor positive breast cancer patient. I mean, their development took, took some time. You know, we’re talking about, I think for Tamoxifen whole process ranged in the order of about 15 to 20 years from, oh, look at that. The cancer has hormone receptor, uh, receptors on the surface of the cells.
Um, and all that turned out to be estrogen receptors. All the cancer is taking estrogen as a mechanism of survival. We can mimic estrogen by giving a, you know, a, a scarred version, if you will, of estrogen to patients that are fit. Where estrogen is setin but not, is not gonna work, um, you know, for the cancer cell and therefore the cancer cells die.
That sounds like a [00:31:00] great idea. Let’s test it in mice. Let’s test it in more bigger mammals. Well, that drug appears to have significant activities to bring it to humans. And that whole process, you know, took about, you know, 20 years. Then by the late 1980s, Tamoxifen was tested in one of the larger clinical trials, and it showed how um, you know, uh, survival benefit.
Dorothy: Right. It changed.
Dr. Elkhanany: Incredible.
Dorothy: Yes.
Dr. Elkhanany: Incredible. Immediately day and night. You know, a couple of years later, people were not dying of breast cancer, anti her two therapy. Herceptin has some, you know, the iber of all melodies, you know, had a whole chapter about that, and I think it was fantastic to see how this saved patients from deathbed. Literally.
Dorothy: Did. I, I remember when that was a death sentence.
Dr. Elkhanany: They were going in, uh, hospitals in UCLA and another hospitals in Los Angeles and looking for patients with HER2+ breast cancer [00:32:00] who have like liver failure or this, and they will given Herceptin to these patients. And it will reverse their disease course. It was magnificent.
Dorothy: Truly a miracle, and I’m so glad that you’re seeing things getting better. Not worse.
Dr. Elkhanany: I think things are getting be better. I think that we have more education, more access to healthcare now. There’s definitely more that we’re able to do, but on average everything is slowly shifting up. Um, doesn’t mean that we but we don’t have work to do. It means that we actually have more work to do to bridge the quality gap and the, and, and, and access to care.
Dorothy: And that may be our next, overcoming our next phase in everything that we’re doing in healthcare. Making sure everyone has quality healthcare, like you said.
Dr. Elkhanany: Absolutely.
Dorothy: Well, thank you so much for coming back and being with us today. Giving us some real life [00:33:00] examples of clinical trials and, and the good that they do and how much it really has helped move that, like you said, needle and has saved so many lives.
Dr. Elkhanany: Well, thank you for having me. And, uh, I, uh, think that I, I will be a mess not to direct, you know, not to commend you on the incredible work that you have been doing. Um, being a pillar in, you know, care pathways for these patients, being able to actually, uh, reach to the community, establish yourself as the liaison for the patients when, and for those who are, uh, concerned and maybe unable to or don’t want to, or you know, um, don’t have the education to do what they need to do for their healthcare. But actually be continued to be a leader, continued to be a trusted source, [00:34:00] and, and then developing best ways for their cure and for their health. I think that that was, you know, um, incredibly challenging, but, as you, as I can say, very clearly, incredibly rewarding journey in the same time. Um, so yeah, thank you for everything that you do for the community and continue to do.
Dorothy: Oh, appreciate your kind words. Thank you, doctor.
Dr. Elkhanany: Absolutely.
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