Mike (Host): This is Pediatrics in Practice, A CME podcast. I'm Dr. Mike, and with me is Dr. Kevin Gin from Children's Mercy, and today we are discussing advancing Hope, clinical trials and pediatric cancer. Dr. Gin, thank you so much for sharing your time with me today. You why are clinical trials so critical in advancing pediatric cancer treatment, say compared to adult oncology? Kevin Ginn, MD: Yeah, good morning. Yeah, it is really the same principle. So we need advancements in cancer in general, whether it's adult or kids. We have different challenges, of course, with pediatric cancers, primarily because they're more rare, than adults. So we have more difficulty running those clinical trials to make those advancements because numbers of patient's we need are not necessarily there. The tumor types are different in pediatrics. Compared to adults as well. So, we used to try to bring down clinical targets from adult trials and, try those in children and they didn't always work as well and it was because the cancers are different And we learned that over time, we have the need to, find new therapies because we are. Quickly reaching, kind of maximum tolerated therapy so kids are able to tolerate chemotherapy better than adults in a lot of cases. But we are really beating these children up with a lot of, radiation, surgery and chemotherapy and, And we need better treatments to reduce that toxicity and, and improve survival. 'cause in some instances we're not improving survival even though we are being a very aggressive. Mike (Host): What do you say to some parents maybe who have already enrolled their child in a clinical trial, but it's still in the recruiting phase, it's taking a little longer. how do you explain that, to them And that, that it's important to get the right amount of patient's? Kevin Ginn, MD: Yeah, I mean that comes, comes into play most commonly when parents are waiting on the opportunity to enroll in a trial. 'cause I run earlier phase clinical trials, so the safety. It is so important on those trials with these drugs that haven't been tried in patient's as often, and we're trying to learn safe doses and side effect profiles. So trying to explain to a family that the treatment that they think may be, best for their child may not be available to them at the time they need it because of, of it being closed for safety monitoring. So trying to explain that aspect of it. A lot of families. I think that we can get these drugs outside of the trials And we're not always able to, depending on what stage they are in development. Mike (Host): What are the biggest barriers for families? what do they face when considering enrollment in a, cancer clinical trial? Kevin Ginn, MD: I just mentioned availability. So families are savvy these days and, do their own research online or talk to other family members even other patient's through like connections through social media and connect with other families of the same tumor types. So they hear about these trials at other centers or at our center. so they want the availability of those either locally And we definitely try to do that here at Children's Mercy. getting lots of options for patient's. But still, there's kids that have to travel either to other sites or to our site from a long distance. So the travel And the cost associated with that, because it's not always. covered to support their meals or gas and those sorts of things. Even though we do have some resources, clinical trials have more restrictions on time points, so we don't have the flexibility to say that, yeah, you can come in a couple of days. We really need that time point to be on time for that clinical trial. There's much more strict criteria. Sometimes they have longer time at the hospital, so, spending longer time because we need drug monitoring levels like a. PK levels that have like all day blood draws that they have to hang around the hospital. And then just the burden of navigating options. So there are a lot of options often for a patient and trying to figure out what is the best treatment for that particular patient And what the family understands about those options is, it's hard for families and it's hard for us too, especially when not one clinical trial treatment is necessarily better than the other 'cause we just don't know yet. But trying to figure out what's best. Mike (Host): communication obviously is, so important here. how do you communicate the risks and benefits of trial participation to parents And in ways that build trust? Kevin Ginn, MD: risk is definitely important, especially in these early phase trials, as I mentioned, that have drugs that most of the time in pediatrics have at least had some. Study in, an adult population or previous clinical trials, but there may be drugs that are pretty new and, And we don't know a lot about them, so there's potentially a huge risk. so the fa parents get sort of frustrated with us for not having all of the information, but we are able to at least go through what we know, what the risks are. I try to go through. The known and previous risks and, point out to them which ones I think as a medical provider are most concerning and most risky. The consent forms that are generated include tables that list out what we know about risk and is divided up into less likely. Most likely and least likely. But if you look at those tables, it's overwhelming. There's, hundreds of things listed and not a lot of them make sense to families. And sometimes the things that are least likely to occur can be the scariest thing, and you don't want that for your child. so we discuss, I could discuss the, what we're worried about. What our monitoring plan is gonna be And the safety plans that are built into the protocol and let them understand that, that we know these things need to be monitored, but, but we, need to still, monitor very closely for some unknown side effect profile. So families do take that into consideration. What is the risk? Something like an immunotherapy that might result in significant inflammation and hospital stays that are prolonged or ICU stays versus a, a pill that they take by mouth every day that has lower side effect profile is, appealing to them, especially if we don't know that one's better than the other. Mike (Host): speaking of immunotherapy, how has recent innovations like immunotherapy, precision medicine, how have they changed the design and. Kevin Ginn, MD: the most common ways that I've seen that affect our clinical trials is we are dividing patient's up into smaller and smaller baskets. So, We know a lot more about specific tumor types And we know more about certain targets, but if we have a rare population of patient's of a certain tumor And then we divide that even further by a certain target that's only available in say, 10% of patient's And we have a drug for that, then it's hard to run those clinical trials so there's improved. Kind of nationwide and even worldwide collaboration to try to capture as many of those patient's as possible. and if you miss the one kid that comes in once a year with that tumor type because of availability at the time or some other reason, then you're missing a huge opportunity to learn about it. immunotherapies are a different beast. You know, they have timing restrictions for something like CAR T cell therapies that have to be generated. So I've had patient's that qualified for CAR T cells, yet. The timing of slot availability and ability to generate for that next patient. just the logistics of it can be challenging. And then, as I mentioned, the, the monitoring required for some of those therapies And the, more serious inflammation and, side effect profiles of some of those therapies can be problematic and require prolonged stay. Mike (Host): it seems like as we get more, personalized with our cancer diagnoses and treatments that it is. Is gonna take a global effort then to kind of gather all that data up to make decisions, right? Kevin Ginn, MD: That's right. recently we have a clinical trial we're participating in currently because it's a global trial. They, they're having safety meetings weekly, but because of the, global nature of it, they have to have two a day now because the. The time zone differences they're having one that occurs our time at like 6:00 AM that I'm not attending, but the 3:00 PM afternoon one for the rest of the world. is more appealing of course for me. Yeah. Mike (Host): Yeah, that's interesting. and I'm sure that's gonna be an exciting area that we'll see how, cancer trials grow And in change in design. Um, I gotta ask Dr again. Everybody's talking about it, asking about it. How is AI affecting this? Or is it. Kevin Ginn, MD: I personally haven't seen it. affecting anything here yet? at least at Children's Mercy. I know there, there are, a lot of interest in AI technologies and, primarily the interest that I have in it has been with diagnostics so. Earlier identification of a relapse or better assessment of staging or, response to treatment. So using, computerized AI technology to assess. A scan and instead of having a human eye look at the pictures on the screen, the, computer generate. What is different about this scan compared to the last three scans and being able to pick up on those minute details that might, be missed by someone? So, few years ago, there was a great presentation at a national meeting where they were using such technology and say adult mammograms and being able to. Utilize that technology to pick up on minute breast cancer, that was missed potentially by the radiologist. Mike (Host): How do you ensure families have adequate support throughout all this and resources, during the clinical trial process? Kevin Ginn, MD: children's Mercy, it has excellent resources from a, nursing support staff that are well-trained and certified And in pediatric oncology. we have social work, that can help with logistics of housing. Things like FMLA and time off from work and other community organizations that want to help families and help contribute to, covering some of the costs that, families are incurring. we of course have great physician staff with multi specialty services that are able to, handle, anything that comes our way. but I. I think pediatricians also play a great role in that, especially for those patient's that live some distance away from the hospital. Because we may not always be able to allow a study physical or study labs to be done at an outside facility 'cause there may be restrictions on that. But if I have a kid on an experimental treatment and they live four hours away and there's some something they're calling me with concerned about, then I need. Someone to help me assess that patient, and that's a great thing that the, the local pediatrician can help assess and, and communicate that medical assessment back to us as we determine what's best for that kid. Mike (Host): Looking ahead, what do you see as the most promising areas of research in pediatric oncology clinical trials? Kevin Ginn, MD: I mean, you've already mentioned precision medicine and immunotherapy. I think Those are continuing to be very important. Targets for improvement. just in my career, my, other primary specialty is brain tumors And in the last five or six years, we've seen four or five FDA approved therapies that are, really previously unheard of for brain tumors in pediatrics. And it's based on those specific targets that were identified that we found drugs for. And in doing the clinical trials and finding that there was improvement compared to chemotherapy. And then also interesting is, is something that you may not think about all the time is reduction in therapy. So as we divide these tumors into a. Groups of patient's and can analyze these small subsets. We find ones that aren't doing well with current therapy that need better options, And we of course, are gonna focus on those patient's. But we're also finding patient's that are doing really, really well with current therapy. But are current therapies very toxic? So clinical trials are also trying to reduce treatment. That's a hard sell sometimes to families though, to tell them. Your kid has a really good chance of doing well with current therapy, but it's very toxic, so we wanna reduce it and see what happens. 'cause that of course could lead to, a relapse for that patient. Mike (Host): That's a tough one. That on them, isn't it? So, it'll be interesting to see how you guys navigate, through that over the years. doctor, again, this has been fantastic. Thank you for coming on today. Kevin Ginn, MD: Thanks for having me. Mike (Host): For more information, you can go to C mkc.link. Slash CME podcast. If you enjoyed this podcast, please share it and check out the entire podcast library of topics of interest to you. This is Pediatrics and Practice, a CME podcast. I'm Dr. Mike. Thanks for listening.