In this episode of "On the Edge of Breakthrough: Voices of Cancer Research," host Dr. Monty Pal welcomes Dr. Lee Jones, Head of the Exercise Oncology Program in the Department of Medicine at City of Hope, to discuss how exercise science is helping reshape cancer treatment and care. Dr. Jones shares his journey from the UK to City of Hope, highlighting the challenges and breakthroughs in establishing exercise as a vital part of oncology research.
He explains how the field of exercise oncology has taken lessons from NASA and their work to prepare astronauts going to and coming back from space to improve outcomes for cancer patients throughout their treatment journey. The episode also explores how breast cancer studies lay the groundwork for integrating exercise into survivorship and treatment and they dive into landmark trials.
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Full Transcript
Dr. Monty Pal:
Welcome back everyone to on the Edge of Breakthrough Voices of Cancer research. I can't tell you how excited I am today to have with me Dr. Lee Jones. Lee, welcome to the show.
Dr. Lee Jones:
Thank you so much. It's great to be here.
Dr. Monty Pal:
Now, uh, we just recruited you from Sloan Kettering. We're on the heels of that, and that's huge news, but I think there might even be bigger news, and that is that Oasis is back, right? <laugh>, I mean, this is, this is huge. When, when we met a couple of times ahead of this, I think that was the main topic of conversation.
Dr. Lee Jones:
Well, that's how we bonded <laugh>, you know, over, over English, britpop music.
Dr. Monty Pal:
I love it. And that's actually probably a great way to kind of take us to the start. So obviously your roots are not here in the us. Tell us about your origin story.
Dr. Lee Jones:
Yeah, so I was, um, born and raised in a city called Stoke on Trent, which is right in between Birmingham and Manchester.
Dr. Monty Pal:
Okay.
Dr. Lee Jones:
Um, it's the West Midlands in, in the uk. So that's, uh, that's a city that was dominated by, by two industries, which was coal, coal mining in, in pottery.
Speaker 3:
So
Dr. Lee Jones:
That's where all like Wedgewood pottery comes from, real Dalton pottery, if you've, if you've ever heard of. Of course.
Dr. Monty Pal:
Yeah. Yeah.
Dr. Lee Jones:
So I, I was born about five minutes away from the, from the factory. And so my dad's side of the family all were miners. My mom's side were all in what we call the pottery industry, the pots. And so that's, that's where I, that's where I grew up. And, you know, academics wasn't really a thing. You know, I, what I wanted to be was a professional soccer player, a football player. 'cause that's what you do, you know, growing up in the north. Um, and then when Oasis came on the scene, you know, I wanted to be a, you know, a pop singer, a rock star. So, um, those things didn't, didn't quite work out. So <laugh>, I, I turned to academics and, and so ended up going to, to university. I really wasn't on the cars. It wasn't in my trajectory at all. Um, so I ended up going to university in the southeast coast
Dr. Monty Pal:
In Brighton. Right. In
Dr. Lee Jones:
Brighton, yeah. Which, Brighton's a beautiful place, um, which is about a four hour drive from Stoke on Trent.
Speaker 4:
Okay.
Dr. Lee Jones:
So that doesn't seem like very far, but in England that's a, it might as well be, you know, might as well have been in the us. That's how far it seemed away. So I was there for, for three years, did my undergrad in, in exercise science. Um, and then after that I moved back home. So I was 20, 20, 21 at the time. Um, and just started working, doing local jobs. There's not many jobs that you can get with a exercise science degree.
Dr. Monty Pal:
Sure.
Dr. Lee Jones:
Um, so that, that's what I was doing. I was playing soccer for my local team and, you know, having a, having a good time. Okay. You know, I, everything was, was okay. And I thought that's, this is, you know, I, this is where I'm gonna be. It's where all my family is. Nobody's left. It's where everybody is. Um, anyway, I was working in this job and this, um, I just got talking to this, this guy, and he is like, so, so what are you doing? I'm like, well, you know, I'm just doing my job. And he's like, no, what, what are you doing here? And I'm like, what do you mean? He's like, is this it for you? And I'm like, well, I, I don't know, maybe. And he's like, didn't you strive to do something else? I'm like, well, I've always interested in doing my graduate degrees, my master's degree. He's like, so why don't you? So this kind of stuck with me. And, um, long story short, there had been a professor who came over to my university in Brighton who was in Canada, and always said to me, if you, if you ever want to do your master's degree, just let me know.
Speaker 4:
Okay.
Dr. Lee Jones:
So literally I went home that night called and said, you know, you probably don't remember me, you know, but you, you said this one time. She's like, oh, Lee, how are you? Are you interested in doing your master's degree? I'm like, yeah. They're like, okay, this was July. You're like, well, you can start in September. So I remember we live in a relatively small house. I walked downstairs, I said to my dad, mom and dad. I'm like, I think I'm going to Canada. And my dad's like, yes. My mom just went white <laugh>. Okay. She goes, and, um, anyway, I ended up moving to this place called Thunder Bay.
Speaker 3:
Mm-hmm
Dr. Lee Jones:
<affirmative>. Which not many people have heard of. It's Northwest Ontario. It's a 14 hour drive from Toronto. Wow.
Dr. Monty Pal:
Okay. So fairly remote.
Dr. Lee Jones:
Fairly remote. It's the closest city is Minneapolis, which is six hours
Dr. Monty Pal:
Away. Okay.
Dr. Lee Jones:
So it's IC Superior. So I went there to do my master's degree in Kinesiology. Um, and quite honestly, didn't really learn too much. Um, you know, when I got there, I remember seeing all my friends while I moved in Canada. I remember getting on the plane and we, you know, were landed in Toronto. And I'm just like, what have I done? <laugh>, <laugh>, what have I, because the professor I knew who told me to come across was doing a sabbatical in the uk. So I knew nobody.
Dr. Monty Pal:
Okay.
Dr. Lee Jones:
And, you know, literally I had my, um, my stereo and my leather jacket. You know, I've got my definitely maybe CD <crosstalk>,
Dr. Monty Pal:
I that. Oh, awesome. Okay.
Dr. Lee Jones:
And, um, so anyway, I, I, I was there and, and it was, yeah. The first few days was, was pretty rough. And then I, um, I taught his, I started to teach the soccer class.
Dr. Monty Pal:
Okay.
Dr. Lee Jones:
Of course, you know, you got the, the bread who comes across, they teach the soccer class, of course. And, uh, there was a, there was a person who was also working with me. He was a local, uh, local fella and, um, of Italian orange. And he is like, what do you do? Why don't you couldn't live with my family? So they took me in, I ended up living with his family, and, um, we've been kind of friends. They kind of looked after me.
Dr. Monty Pal:
Okay.
Dr. Lee Jones:
And so I was in indoctrinating into the Italian culture, which was just unbelievable. And so I was only, I was there for two years, and after that, you know, I had two choices. Right. Really, I either go back to the UK with this master's degree in kinesiology that probably nobody would recognize, or I could do my PhD. So I'd applied to a bunch of PhD courses in the US as well as in Canada, and got rejected from every single one.
Speaker 3:
Hmm.
Dr. Lee Jones:
So, you know, I thought, okay, that's, that's it. I guess I'm going back to the uk, but I hadn't heard from one place. And this was the University of Alberta in Edmonton. So I called and said, you know, I know I'm not in, but I just want to confirm before I book my ticket back to the uk. And they're like, oh, you haven't got your letter? I'm like, no. They're like, well, you've been accepted. And I'm like, no, this is Lee Jones <laugh>. They're like, no, you've been accepted, um, by this new professor Kerry Kye. Now this will, this will become extremely relevant because Kerry Kye was the first author on the New England paper.
Dr. Monty Pal:
Wow. What a small world. Okay, keep going.
Dr. Lee Jones:
Yeah, keep going. So, so Kerry accepted me. So I, you know, I moved from Thunder Bay to Edmonton, which, you know, I went from a city of 50,000 people to a city of a million people. Um, so it, it felt like, oh, this is fantastic. U University of Alberta is a huge school, 30,000 undergrad.
Speaker 4:
Right.
Dr. Lee Jones:
Um, so I went there and, you know, got a bachelor pad, started my PhD, um, was playing soccer as well for the university team at the same time. Okay. So I was traveling, you know, trying to balance both. Um, we would, you know, I work on the week, and then we'd travel on the weekends. We fly to, you know, Vancouver, Victoria, Saskatchewan. It was, it was great actually. Um, and then we, you know, Kerry just got his first NIH grant, uh, in exercising cancer, colorectal cancer, as had it happened.
Dr. Monty Pal:
Okay.
Dr. Lee Jones:
And so, you know, I was the, the PhD student working on that project. So I'd be the exercise physiologist, I'd be the clinical research coordinator. Um, and so that was, that was my training. I'd be over at the cancer center, you know, in, in the, basically in the labs in the, in the consults with the oncologist. And this is where I learned oncology. And so, um, basically I was, I was there for four years, did my PhD there, there was no jobs at that time. So I stayed on, did my postdoc
Speaker 4:
Okay.
Dr. Lee Jones:
For another two years. That's when I started kind of developing my own research interest. Even at that time, I wasn't sure if I wanted to be a researcher. And at the end of that, I got offered, uh, a job at McGill or at Duke. And so I was married at that time as well. I got married, um, to a Canadian lady, um, which was great. And, and I said, well, I had to go to McGill where I have this tenure track position, but I had to do some teaching. I knew I didn't want to teach, or I could go to Duke. You know, I have this, um, basically a three year contract. And by the end of that three years, I had to be a hundred percent funded from grants. But I'm like, well, you know, three years at Duke, that wouldn't look bad on my, on my resume. So we decided to go to Duke. So we drove down from Edmonton to North Carolina. We left on Boxing Day, so December 26th in Edmonton. It was minus 26
Speaker 4:
Uhhuh <affirmative>.
Dr. Lee Jones:
And, and then we were golfing in North Carolina on New Year's Day.
Speaker 4:
Oh my gosh. I
Dr. Lee Jones:
Mean, just unbelievable.
Speaker 4:
Yeah.
Dr. Lee Jones:
Um, so that was my first job, assistant professor in medical oncology.
Dr. Monty Pal:
And you stayed there for a while, right? I understand you went through associate as well at
Dr. Lee Jones:
Duke? Yeah. You know, the first year was a little bit rough, to be honest. Um, I got, I got a, a few grants, but it just want, wasn't quite clicking in the way that I was hoping it, it would, I come from this environment in Canada where everyone was, I knew everybody. And Duke was a little bit different, um, at first, at least. But then I got my first grants started to build my team, uh, got our first R ones. And so yeah, I was there in the end for I think nine, nine years
Speaker 4:
Or so. Okay. Okay.
Dr. Lee Jones:
And then towards the end of that, my wife went to PA school at Duke. So when she started that, I knew that maybe at the end of that, we, we would start looking around. And so we were, you know, at the end of that, we, we looked at a couple of different places and, um, Memorial s, stone Kettering came, came knocking. And, you know, I couldn't, I couldn't, in my gut it was just the, the right place to go. Um, so we made the move to, to New York City, and I completely rebuilt the team. Um, and MSK was just, you know, it was, it was amazing.
Dr. Monty Pal:
You know, it's remarkable. I, I remember when, uh, it was, so Armenian actually our chair of pediatric oncology. He, he's actually been on this program before. Wonderful guy. He shared your CV with me. And you have just been so prolific in the space of exercise oncology, uh, at a time, I think when there might have been a lot of sort of skepticism, you know, around the field. Uh, tell me about what it was like to sort of build that program at Sloan Kettering. 'cause I, I imagine, you know, we're gonna see a bit of a transformation in our program here with you being on faculty.
Dr. Lee Jones:
Yeah, it was, uh, it was very interesting. We, you know, this is, I was being recruited at just as Jose Alga had started.
Dr. Monty Pal:
Oh, okay. Okay.
Dr. Lee Jones:
And so, um, you know, I met with Jose and I was just, yeah. This, this guy was just a force,
Dr. Monty Pal:
I mean, just for our audience, a storied figure in breast cancer research. Right. And who was really an emerging leader and really had a tragic early passing.
Dr. Lee Jones:
Right. Yeah. He, he did. Um, so there was Jose, there, there was, there's, you know, there's Craig Thompson, there was Cliff Hudis
Speaker 3:
Mm-hmm <affirmative>.
Dr. Lee Jones:
Larry Norton, Howard Cher. Um, you know, and I, I felt that this, this was really an important step for me. I think at Duke, duke was a phenomenal place as well. But I felt that I needed to go to a place that would really challenge me. And I, and I want to be in a room where people are skeptic, skeptical about what we do. And, and, because I think that's what forces you to go to the next level.
Dr. Monty Pal:
Sure.
Dr. Lee Jones:
So I would, I would be presenting, um, you know, cliff would run the breast medical oncology rounds every Thursday morning. There'd be 26 breast medical oncologists in the room. You know, I get up and present and Yeah. There'd be, you know, like, what about this? I'm like, this is exactly what we need. Right. It's exactly what we, you know, it forces us to think differently and not to rest on our laurels and, and really push it.
Dr. Monty Pal:
And can I ask, is it, is it fair for me to say that a lot of our understanding of the role of exercise in oncology kind of begins in in breast cancer? Is that sort of where it has its roots? Or is it more diffuse than that?
Dr. Lee Jones:
Yeah, I think that's where, that's where still 80% of all the research occurs. Mm-hmm <affirmative>. Is in, is in breast cancer. There's probably a few reasons for that. Right. It's, it's a large population. I think it's a population that are very, um, they advocate for, for many different things. And so there's more funding that's typically available that, so researchers tend to, to follow the money. And I think where really exercise really came to the fore was with the development of cancer survivorship. So every, you know, the, in the, I think Institute of Medicine report was talking about, you know, the growing survivorship population in oncology, you know, and, and all the late events that, that these individuals were experiencing, which a large proportion of those individuals were breast cancer survivors. Right. So, exercise coming in to be an intervention to address some of the psychosocial as well, the physiological late effects of therapy. That's where it kinda really found it, found its home. So a that's where a lot of the research started. Um, and then slowly has been moving out into, into other solid tumors a little bit into, into hematology as well. And so I think for us, that's where we had a lot of our grants. We, you know, really were interested in the physiological consequences of breast cancer therapy, particularly because the role of anthracyclines and Herceptin
Speaker 3:
Mm-hmm <affirmative>.
Dr. Lee Jones:
So, when I was in Edmonton, I didn't know it at the time, I didn't appreciate it at the time, but there was a, there was a big, there was a large randomized trial underway looking at adjuvant Herceptin in HER two positive breast cancer, B-C-I-R-G double zero six
Speaker 3:
Mm-hmm <affirmative>.
Dr. Lee Jones:
So, you know, that, um, there was three large randomized controlled trials. B-C-I-I-G was, was run by Dennis Leman.
Speaker 3:
Mm-hmm
Dr. Lee Jones:
<affirmative>. Little, little known, but the clinical trial unit that was run out of Edmonton.
Dr. Monty Pal:
So, you're kidding. So I'll tell you what a small world this is. I actually trained in Dennis Layman's lab at UCLA.
Dr. Lee Jones:
Yeah. So, right. <laugh>. Yeah. So, so Trio
Dr. Monty Pal:
Uhhuh
Dr. Lee Jones:
Was at, its its offices in Edmonton, and was headed up by a guy called John Mackey.
Speaker 3:
Mm-hmm <affirmative>.
Dr. Lee Jones:
John Mackey was the head of breast medicine, breast medicine oncology at the Cross Cancer Institute. So I'd be going across the K Crohn Institute, you know, recruiting individuals for Dr. ER's studies, but I'd be going to rounds, and I got to know John and all his fellows very well.
Dr. Monty Pal:
Okay.
Dr. Lee Jones:
So we were, I remember it vividly. We, we were sitting in a room and he was talking about BCRG. He was talking about double zero six. And he was like, you know, well, there, there's a concern because the combination of anthracyclins with Herceptin, you know, in the metastatic trial that was with this New England paper with, with slayman as first author, I think the heart failure rate was something like 30%
Speaker 3:
Mm-hmm <affirmative>.
Dr. Lee Jones:
Something crazy. So people were really worried about this going into the adjuvant setting. Yeah. These individuals are gonna live, you know, longer. And so there was, you know, as a result of that, there was serial echo cardiac imaging that would occur. And we just got talking. John was saying, oh, we're doing this cardiac imaging. I'm like, okay. Are are you doing anything else to look at, you know, overall cardiovascular, cardiopulmonary health of these individuals? He's like, no, but John is just an amazing guy. He is like, but what are you thinking? I'm like, well, maybe we could do some exercise testing, cardiopulmonary exercise testing, maybe do some exercise echo to really get, um, a better understanding of what might be going on to the hearts of these ladies. Because, you know, if you just look at rest in ef, it's, you know, by the time you see a, a reduction in ejection fraction in some regards, it's already too late.
Dr. Monty Pal:
Absolutely.
Dr. Lee Jones:
So he's like, okay, well, let's do it. And now we got funding from Roche to do, like, the first exercise echoes in a population of women who were in oh zero six. So we had, you know, we had individuals who were just getting AC or a CT individuals who are getting just a CH and then A CTH. Um, and so we would be able to profile 'em. And of course, what we found is the cardiovascular risk profile that patients get in Herceptin with the antracyclines was worse than any of the other two arms. So the first paper to come out in oh zero six is our little paper in Cancer Epidemiology, biomarkers and prevention. And then the New England paper came out. Um, so that's, that's kind of where it all started for me. It was, was that that's study
Dr. Monty Pal:
That, that's remarkable. So I have to tell you, and this is a little bit of oncology lore at this point, perhaps, but, you know, I just remember those initial studies. Dennis Leman walked into a lab meeting when B-C-I-R-G oh oh six came out and was so excited about sharing with us in the small room the results. Right. You know, hot off the press. But I do remember the debate that emerged from this around use of anthracyclines Yep. With Trastuzumab and, you know, the different camps. It was almost, uh, an east coast, west coast difference in philosophy where, you know, on the East Coast, for instance, folks like Cliff Hudis and Larry Norton were arguing, you know, again, for use of anthracyclines Yep. And combination with Trastuzumab on the West coast, you've got folks like dentists and others really arguing for a really, uh, uh, docetaxel and Paclitaxel based regimens. Right?
Dr. Lee Jones:
Yeah. Non non-line. Yeah. And I think in that trial, I think it was, um, there was a slight, I think, disease-free survival benefit of A CTH, but I would agree with Slayman that that was offset by some, the increase of cardiotoxicity. Yeah. So I think overall, you know, but of course it wasn't powered to directly a comparison. I think that's what New England paper said. So it was kind of left, left out there, but I think as, as history is, it's continued, I think, you know, there's less and less use of anthracyclines in, in that setting. Exactly. That makes absolute sense.
Dr. Monty Pal:
Yeah. Yeah. That's, so this kind of takes me to, you know, the studies that you've sort of built, not so much to sort of dovetail on existing trials, but really independent studies that you've designed assessing exercise oncology, right. Exercise physiology, um, as a means of maybe improving cancer outcomes. You know, I've read some of your studies in the context of not just breast, but prostate cancer. Give us a sense of your philosophy around why we need studies that are evaluating exercise like anti-cancer strategy.
Dr. Lee Jones:
Yeah, I, I guess the, the context there is, is what I just mentioned with starting in double zero six and looking at more of the cardiovascular physiological consequences. Mm-hmm <affirmative>. So, you know, that's the first half of my career was focused on, on that very question. Um, and as we were doing more and more work in that, in that arena, you know, we'd have individuals in, into our trials and they'd say, Lee, you know, I, I'm feeling bad, but what's happened to my, to my cancer? And I'm like, what? What do you mean? Like, well, I'm fit now. Does that means, is there less chance of my cancer coming back? Does this mean that I'm gonna respond better to the therapy I'm getting? And I'm like, I, I don't know. Okay. <laugh>
Speaker 3:
Sure, sure. We,
Dr. Lee Jones:
We don't know. Nobody, nobody's really thought about it from, from that perspective. It's really been from symptom control perspective. So this is right around the time when I was leaving MSK to come, I mean, leaving Duke to go to MSK.
Speaker 4:
Okay.
Dr. Lee Jones:
Um, so I, I decided that time that, you know, we, if we're putting together this exercise oncology program, we really needed two, two arms. We needed to continue our work in what we've been doing on, on focus on the physiological consequences. I recruited an investigator from NASA to kind of take over that side of the program
Dr. Monty Pal:
From nasa.
Dr. Lee Jones:
Yeah.
Dr. Monty Pal:
Okay. Tell me about that.
Dr. Lee Jones:
Well, there's, there's a long story there because she's Canadian and she was a intern Okay. In Kerry's lab, but basically, you know, helped me get, you know,
Dr. Monty Pal:
Photocopy. Fair enough.
Dr. Lee Jones:
So we have a long, long history. She went from Edmonton where she was doing undergrad to UBC to her master's in PhD, and then went to NASA to work on basically the physiological consequences program.
Speaker 4:
Okay.
Dr. Lee Jones:
So the, a mandated strategy for all astronauts go into space is exercise. Okay. They exercise them in space.
Dr. Monty Pal:
I see the connection now. Okay.
Dr. Lee Jones:
So this might sound a little bit strange, but a lot of the consequences of zero gravity are very similar to the cons, the physiological consequences that occur in individuals going through cancer therapy.
Dr. Monty Pal:
Well, I would've never drawn those two together.
Dr. Lee Jones:
Yeah. It's, it's, it's uncanny. Actually, we, we published a paper, I, I'll send you the review on this, please. Yeah. Did the comparison. It, it's, I actually think it's pretty fascinating how it was recognized very early in the first NASA flights in the sixties that the physiological consequences was something they needed to address. So they first, what they first characterized it, then they started to intervene. And this is right at the same time that we're coming up with the first poly chemotherapies. And of course, we recognize the physiological consequences very early, but in oncology, for whatever reason, we didn't, we didn't try to intervene to, to stop that route. Yeah. The way that we intervened is by doing dose reduction or, you know, therapy
Dr. Monty Pal:
Discontinuation. Sure.
Dr. Lee Jones:
A very different approach. Um, so we kind of parallel like what happened with nasa and then what happened with oncology, and could we, can we now learn from what, how NASA thinks about basically prehab rehabilitation and then rehabilitation, because
Dr. Monty Pal:
Okay.
Dr. Lee Jones:
As astronaut, as soon as astronaut know, they're going on a mission, they will start training them to get 'em as fit as possible before they go on the mission. They then train them during space, and then as soon as they come back down to earth, they training and they train 'em until they reach their pre-flight physiologic status.
Dr. Monty Pal:
Okay.
Dr. Lee Jones:
Imagine if we applied that model to oncology. Anyway, um, I, I digress a little bit, but we, I was thinking about those kind of questions and then, you know, the patient's coming up to us and asking us question. So, so when I went to MSK, I'm like, you know, we made the decision, we we're also gonna create this new arm of our program, which for me was like starting again.
Speaker 3:
Mm-hmm <affirmative>.
Dr. Lee Jones:
You know, I, I've got a background in exercise physiology, but I don't have a background in, you know, cell biology. I don't have a background really in, in oncology per se, other than what I picked up from, from medical oncologists.
Dr. Monty Pal:
Sure.
Dr. Lee Jones:
Um, so it really, I guess, you know, for me, I really need to, to think about this. And, and the way I thought about it is, you know, I think it was, was hang around with, again, the medical oncologist, and particularly with John Mackey and others developing these clinical trials. And I'm like, well, I think that's what we need to do from an exercise perspective. We, we need to think about the development of exercise, like we would the development of a drug.
Speaker 3:
Mm-hmm
Dr. Lee Jones:
<affirmative>. And so the first thing I try to do when entering new areas is try to put like a framework together rather than just, you know, going straight in and try and do these trials that could be a little bit haphazard. You know, what is the, what is the philosophy? What is the conceptual model that we're, you know, that we're working along to try and develop these questions. So I felt that we needed like a drug development pipeline. So when we started the, this era of research, this was back in really in earnest back in 2015. The first thing is published this translational framework. And so, you know, going from epidemiologic studies into preclinical studies into phase one type studies. Now, phase one studies have, have never been done with exercise in any clinical population, let alone oncology. But I felt, you know, I think time and time again, we see trials of things like metformin or vitamin D or Omega-3. Um, we see these big phase three trials, you know, looking at risk of recurrence.
Dr. Monty Pal:
Right.
Dr. Lee Jones:
And what do we, what, what typically they fail.
Dr. Monty Pal:
They fail. Yeah. They
Dr. Lee Jones:
Fail.
Dr. Monty Pal:
Absolutely.
Dr. Lee Jones:
So, so why is this? Is this because they don't work? Is this because the trial design has been suboptimal in some way? Um, is it because we don't know the right population? We don't know the right dose. And so if you look at all these trials, they've basically been designed on the basis of epidemiologic findings, which I don't, you know, given self report or another, I don't think you can use that information to then design a clinical trial. You would never do that with a drug mm-hmm <affirmative>. Right. You wouldn't ask individuals what they've been taking to, and then say, well, okay, based on that, we think we should, this is what No, you'd, you know, you a very rigorous approach. So we basically tried to do the same thing. Um, so that's, that's where it came from. And, you know, I, I live in the oncology world and so, you know, our research looking at physiological consequences, I think that's, that's gonna move the needle a little bit. Um, but I think to really make this part of part and parcel of standard of care therapy, then we need to be designing trials with the same endpoints as the oncologists do. We need to speak the same language. You
Dr. Monty Pal:
Need to look at recurrence overall
Dr. Lee Jones:
Survival, all these PPCR overall survival, relapse rate, um, you know, because that's the world in which I live. Yeah. And I think if we really want to get oncologists on board, then they're the kinda studies that we need and, you know, we need to be publishing in New England and these others. And then you read that side by side and you say, okay, that's the evidence we need. It's not the evidence that's gonna convince me. It's the evidence we need to convince to convince you.
Dr. Monty Pal:
Sure.
Dr. Lee Jones:
Um, so that's really where we, where we came from, and that's the way that we've tried to approach it.
Dr. Monty Pal:
Brilliant. You know, speaking in New England, you brought it up. So, you know, this challenge study that was just published there, huge waves in the oncology world. It was one of the highlighted presentations at our ASCO meeting this past year. Um, it was led by, I didn't realize this prior to discussion today, you know, your former mentor Yeah. You know, Carrie <inaudible>.
Speaker 3:
Yeah.
Dr. Monty Pal:
Um, excellent study. Would love to get kind of your take on it. And, and just in case our audience isn't familiar, maybe you could sort of spell out the design a little bit and some of the primary results.
Dr. Lee Jones:
Yeah. So the challenge trial was basically designed back in 2007, 2007, 2008. Wow. And it was designed on the basis of two epidemiologic studies, both published by Jeff Meyerhoff, actually in the same issue of the, of the JCO in 2006. So, so Jeff had had, I think they got data from a randomized trial where they collected self-reported exercise. So Jeff come along and said, well, you know, let's look at the association between how much exercise these individuals were reporting and the risk of colorectal cancer mortality.
Speaker 3:
Mm-hmm <affirmative>.
Dr. Lee Jones:
And, you know, these were in sample sizes of like 600 and maybe 800 individuals.
Dr. Monty Pal:
Okay.
Dr. Lee Jones:
Uh, so these are not huge epidemiologic studies, but they found a, a, a hit. Okay. They, they, they got, they, they found an association of individuals who were reporting, now don't wanna get too much in the weeds, but those who are reporting around about 18 met hours of exercise a week, 18 met hours of exercise a week is about 300 minutes of moderate intensity exercise a week.
Dr. Monty Pal:
Okay.
Dr. Lee Jones:
So an hour a day, you know.
Dr. Monty Pal:
Got it. Okay. Days. I'm just doing the math in my head. Okay. Got it.
Dr. Lee Jones:
Um, any, any exercise levels, doses below that didn't, weren't associated with, with colorectal cancer. Um, colorectal mortality. And then interestingly, if you went above that, it was of a plateau. Okay. It wasn't a dose response.
Dr. Monty Pal:
So you don't just do more and more exercise. Yeah. You get more and more benefit
Dr. Lee Jones:
Per se. Yeah. It's that, I mean, maybe we can talk about that a little bit later. Um, you know, if we, if we had cardiovascular death as an endpoint, you typically see this very nice linear dose response when it comes to cancer outcome. You don't.
Dr. Monty Pal:
Interesting. Okay.
Dr. Lee Jones:
We've seen that now time and time again. I do think there's this like threshold, actually. Um, but maybe we can talk about that.
Dr. Monty Pal:
Yeah, you got it.
Dr. Lee Jones:
So, so there was, there was two epidemiologic studies. So on the basis of that, what do people say? Well, they say, you know, that's interesting. You know, the, the associations, it was like, if, you know, a 40% reduction in the risk of dying from colorectal cancer after controlling for things like BMI stage disease treatment. So this was, um, so people say, well, that's, that's an association. You know, the observational data is the weakest form of evidence we have. It's not, it's not causal. So the only way we're gonna actually prove that exercise does have a mortality benefit is to do a phase three randomized control trial. In my view, this, that's a colossal leap, right? Mm-hmm <affirmative>. That's, you're going from these epidemiologic studies to do now designing these phase three trials, which is exactly what we've been doing for things like metformin, omega threes
Speaker 3:
Mm-hmm <affirmative>.
Dr. Lee Jones:
Every vitamin vegetable intake. And again, they've, they've typically failed. So, you know, I've, they were doing the same thing. So the challenge trial was, um, the primary endpoint was disease free survival. It was, I think it was in, I think the original design was almost a thousand stage two, stage three colorectal cancer patients. Um, and this is, I, I guess I look at this as extended adjuvant therapy because all these individuals had to have finished their primary definitive therapy, and then it was randomized action to, to exercise or not.
Speaker 4:
Right.
Dr. Lee Jones:
For a period of three years. Um, now, so, or not, so it was a control group. They got health education, which was basically some physical activity advice. And then in the intervention group, basically they got, um, supervised exercise for the first, I think it's like, correct me if I'm wrong, I think it was the first three to six months. And after that it was a home-based program. That's my
Dr. Monty Pal:
Understanding too.
Dr. Lee Jones:
And so what did the data show? Well, there was, um, disease-free survival benefit significant and a overall survival benefit. And, you know, I think in the region of 30% improvement, I think in, in DFS, um, I think similarly with, with overall survival. And, you know, quite honestly, I was, I was surprised. I've gotta be honest. Yeah. I, I was expecting it to be, to be negative.
Dr. Monty Pal:
Okay.
Dr. Lee Jones:
Um, and, and so, you know, on the whole, I think for the field, it's, it's, I mean, it's been, it's been a huge job. I mean, the coverage that it's got has just been incredible. I was getting text messages from all over the planet <laugh>, just like,
Dr. Monty Pal:
I think I was one of those
Dr. Lee Jones:
Techies
Dr. Monty Pal:
To get your take on it. Right. Just like
Dr. Lee Jones:
I be, you know, look, look at this data. This is, this is phenomenal. So I was very keen to, very eager to, to read the paper.
Dr. Monty Pal:
And I will say that in our discussions, you brought up a couple, and, and this is important in any, you know, sort of academic setting to have really sort of a healthy debate around some of the fine points of the trial. You know, one of the things that we sort of touched on in our discourse was, was sort of the duration of accrual, right. Uh, 15 years, is that right? To really get the study from start to finish?
Dr. Lee Jones:
Yeah. And I, I think this is, um, this is a problem that we have with behavioral trials, right? Mm-hmm <affirmative>. So the way this is originally designed is because of the supervision aspects. Then in the sample size required in the length of intervention, then you can only recruit from sites that have the ability to be able to administer exercise at high fidelity,
Dr. Monty Pal:
Let's say. Right? Right.
Dr. Lee Jones:
Um, and so in colorectal cancer, you know, historically they, those trials with exercise have been hard to accrue to. So, and I think this was reflected here, you know, it was, um, a long duration. I know it was a, it was a tough slog, and I think it got a standing ovation at asco. I think more as much as for the results, as for the persistence. Yeah. <laugh> is, but of course, that raises some issues, of course. 'cause, you know, standard of therapy changes can change a lot during that time.
Dr. Monty Pal:
Absolutely.
Dr. Lee Jones:
They defended in the paper, said didn't change that much, and maybe they were fortunate to get away with that, but of course, the outcomes in the control group were better than, than expected. But that's, that's gonna happen over a 15 year period. Outcomes are gonna get better. So, you know, I think the le that, that tells you that, that type of approach, people might say, well, you don't need to do supervision. Everything can be home-based. Um, but I think that also raises question about delivery of, in quantification of the actual exercise intervention itself, which I think is something that's, we, we don't talk about enough. And, and that,
Dr. Monty Pal:
If I recall correctly, was really based on self-report in many cases in this study, which I, I think probably comes with its own caveats.
Dr. Lee Jones:
Yeah, exactly. So I think there was an important caveat. This, um, the, it it, it said in, in the paper that they, they recruited non exercising individuals. Yeah. And I think this is a really important point because if you think about eligibility for a drug trial, then typically individuals coming to drug trial, I've had no prior exposure to that drug.
Dr. Monty Pal:
Right. Right,
Dr. Lee Jones:
Right. And in fact, if they've had prior exposure to any drug that we think even might be related, they're typically ineligible. Right? Yeah. Because can we really interpret, you know, the new administration of this drug on, on disease endpoints? And in this case, so what we've tried to do is try to recruit non exercising individuals. You know, if individuals are already exercising, they're already taking the drug. That's particularly problematic in a randomized trial. If they get randomized to a control group, now you've got contamination.
Dr. Monty Pal:
Exactly.
Dr. Lee Jones:
So the differences between the intervention and the experimental and the control group are minimized. So, so what happened here? So they said they ex they recruited non exercising individuals, but the mean met value of exercise at baseline was something like 11.5 mets.
Dr. Monty Pal:
Mm-hmm <affirmative>.
Dr. Lee Jones:
Nine met hours a week is 150 minutes.
Dr. Monty Pal:
Okay.
Dr. Lee Jones:
So these individuals were already doing the CDC guidelines at baseline.
Dr. Monty Pal:
Got it.
Dr. Lee Jones:
Um, so, you know, you've got a, you know, you've got a very active population coming into this study. They got, they got, they went into, you know, either the control or the exercise group. And the goal of the exercise group was, you have to look at this a little bit differently because the goal was to increase the amount of exercise by 10, met hours above what they were doing at baseline. Mm-hmm <affirmative>. So this, so I think people look at this and say, well, the intervention, it was only like yet to do three to five days a week, about 45 minutes. That no, it was that on top of what they were already doing.
Dr. Monty Pal:
Right.
Dr. Lee Jones:
Basically doubled the amount.
Dr. Monty Pal:
Okay.
Dr. Lee Jones:
And so what happened, the control group was still reporting, actually, they increased their exercise behavior a little bit actually across the course of the study. So they, they were exercising consistently throughout the study, the control group, but the exercise group was doing more.
Dr. Monty Pal:
Okay.
Dr. Lee Jones:
And so I don't think this was a comparison of a sedentary versus exercise group. I think it's different levels of exercise. And you're right, the, there was a supervised portion, but adherence to that supervised portion was actually poor. Um, and then it was self-reported compliance to the exercise intervention. But the exercise intervention was also reported as individuals were able to do any dose, any modality, any intensity that they wanted to do. Um, and they got, you know, and again, it, it worked, right? Mm-hmm <affirmative>. But again, if you think about that from a drug context, imagine you doing a randomized trial where you said, well, you know, you can take any amount of the drug that you want, <laugh>, you know, over, above the amount that you are already taking. So I, I think, um, you know, there's, there's some caveats that come along with that. And so I think this was, was a case of, um, an intervention that tested a higher level of excise relative to a group that was, was already quite active, um, to begin with.
Dr. Monty Pal:
You know, I'll tell you, I think the challenge study, which as you'd mentioned, has gotten so much press, you know, it does have those flaws. And it actually in some ways, uh, leads into, I think some of the, the benefits in the DR testing strategies that you've devised for exercise oncology. I've had a chance to read through several of your papers, and I've got a flavor for, you know, the methods of administration of your studies, the sort of the tested hypotheses and so forth that maybe this is a good opportunity for you to sort of dive in and tell us how, how we can sort of ameliorate some of these issues that studies like challenge from.
Dr. Lee Jones:
Yeah. And, you know, don't get me wrong. I think challenge despite, you know, I, I, I completely agree with you. I think the debate is, is a healthy debate. Yeah. I think we, I think it's our, I think we should be debating these studies just as much as we, as we were the drug study. I know there's like, well, when it comes to exercise or, or you know, diet people like, well, you know, it's, this is, these are so good that, but no, I think the only way we can get better right? Is, is to really critique these studies in a way that we will critique any study. Of course. So I think it, of course, I think it's healthy to do that in, you know, I think my view of every trial has limitations. There's no, there's no such thing as a is a perfect trial. Yeah. So I think despite some of these caveats, um, you know, it was a positive. So it was a positive source. So I look at this and, and say, well, imagine if we were able to address some of these limitations, maybe the benefit is even better then, you know,
Speaker 3:
Agreed. So,
Dr. Lee Jones:
So I think that's, that's the way that I think we, we, we should look at it. Um, so what, what we try to do is, again, tra really adopt that drug development approach and try to understand, you know, I think key prerequisites to then to basically do the optimal study design. So when we get to a phase two definitive trial, we know what the dose of exercise should be. We know how, what the duration should be. We know what the schedule is, we know what the right patient population is, and I think we have a mechanistic understanding of how it might be working. Um, so that's, that's what we tried to do. And again, we, we can glean some of this information from, from observational studies. It's not perfect, but we can, we can start there. We can get, obviously get into our mouse studies, which of course have their limitations as well. Right. But we can start looking at dose response. Um, and I think we've, we've, we and others have, have started to tick some of those, some of those boxes. And so where I, where I felt where we needed to go is to do these kind of like phase one equivalent type trials.
Speaker 4:
Yeah.
Dr. Lee Jones:
Um, because we, we need, again, we need to first I think have an antitumor biological signal for exercise. Before we would design a trial on a hard endpoint like P-F-S-D-F-S or PCR, we first need some indication that exercise has any antitumor efficacy at all in a, in a human right. Well, I a
Dr. Monty Pal:
Signal, I wonder if maybe we can discuss this in the context of one of your published reports. And I, I'm thinking about your jam oncology paper looking at prostate cancer. And I, I, I, you know, saw that title incorporating the term phase one, and I, I really read it with a lot of interest <laugh>. So, so maybe you can tell me a little bit about how that study in particular was structured.
Dr. Lee Jones:
Yeah. So we, what the, there'd been a few epidemiologic studies
Speaker 3:
Mm-hmm <affirmative>.
Dr. Lee Jones:
Um, looking at the relationship between post-diagnosis exercise and risk of prostate cancer mortality and showing a, showing a benefit.
Speaker 3:
Mm-hmm <affirmative>.
Dr. Lee Jones:
A pretty significant, but again, same kind of thing with, with colorectal cancer, it's observational. So, you know, what, what, where do we go from there? And I didn't feel that we, we we should make that leap.
Speaker 4:
Yeah.
Dr. Lee Jones:
And do a phase three trial. Um, I'll just mention the caveat there, there was a phase three trial that was launched called the, I think it was called the interval trial, which was a phase three trial of exercise and resistance training in men with, uh, metastatic castrate resistant prostate cancer.
Dr. Monty Pal:
Okay.
Dr. Lee Jones:
But that closed early due to, um, lack of accrual. Interesting. I didn't know that. Anyway, so, so that was going on in parallel. And we thought, and we were, you know, that study came to Ms. K and said, do you wanna be part? I'm like, I don't think we're, we're ready for that.
Speaker 4:
Yeah.
Dr. Lee Jones:
So we decided to take the, the slower approach, if you will. Um, so yeah, so we had some preclinical data suggestion also, and there might be a signal. And so I, I felt that we, you know, there was, there was a decent rationale of why we should launch a phase one trial in localized prostate cancer. And so I'm like, okay, you know, if we're gonna design a phase two trial, again, we, what, what is the dose
Speaker 3:
Mm-hmm <affirmative>.
Dr. Lee Jones:
That we should be using? Should we even do a phase two trial? What if there's, if there's no signal at all, then why, why we even do a trial in the first place that, you know, that would be the go no go decision. Right. We'd, you'd stop the development. If that was a drug, you'd stop it right there. Right,
Speaker 4:
Right, right.
Dr. Lee Jones:
You do a phase one, if it's not safe, if it's toxic, you stop. If there's no signal, you stop.
Speaker 4:
Yeah.
Dr. Lee Jones:
So we, we go into these studies with the same kind of mindset. And so, you know, I, I thought prostate cancer was, had a good biological rationale of why we would go in there. And then the other, the other, and the way I thought, I thought we could design that is, you know, if we need to get to the tumor right. To look at anti-tumor activity, once you apply that filter, there's only certain settings in which you can do that on an oncology. 'cause most of the time it's either getting neoadjuvant therapy, so it would be confounded by the effects of other anti-cancer therapy. Or it's in the adjuvant setting where there's, there's no tumor to assess. You can use CTD NA, but I'm not sure it's quite sure if it really for prime time. Sure.
Speaker 4:
Yeah.
Dr. Lee Jones:
So, you know, we, we loot in, um, we thought maybe these, these preoperative window of opportunity studies might be a setting in which we, we could do this. So I spoke to the, some of the surgeons at MSK, and they're like, I'm like, what, what window can you give me? Like, and they're like, well, probably three to five weeks. I'm like, done. We, let's,
Speaker 4:
Okay,
Dr. Lee Jones:
Let's do it. Let's do it. So the idea was that we would take these men non-exercise in men all scheduled for their radical prostatectomy, and we would exercise them in the window. We would exercise 'em from as long, from the point of diagnosis until their scheduled surgery. We wouldn't, we wouldn't delay surgery in any way at all.
Dr. Monty Pal:
Okay.
Dr. Lee Jones:
So we just use that, that window that they, that they had.
Dr. Monty Pal:
Okay.
Dr. Lee Jones:
Does this make sense?
Dr. Monty Pal:
Absolutely. Kind of your classic window of opportunity study, if you will.
Dr. Lee Jones:
Precisely.
Dr. Monty Pal:
And, and we do this in drug design all the time.
Dr. Lee Jones:
Yeah, yeah. Yeah. So it's, it's not something that I created. Yeah. It's something that you use in drug development all the time. So I, I felt that, okay, could, can we do this? And so the idea was that within that window we can, we can look at escalated doses
Speaker 3:
Mm-hmm <affirmative>.
Dr. Lee Jones:
So we thought, you know, maybe we can use, um, you know, a three plus one design, you know, a different Yeah. You know, so I sure started reading about phase one trial designs. Uhhuh <affirmative>, it's for a drug guy called Dave Hyman. I dunno if you know Dave Hyman. I
Dr. Monty Pal:
Know David Very, yeah. Absolutely. Terrific drug developer
Dr. Lee Jones:
Actually. Oh yeah,
Dr. Monty Pal:
Exactly. Huge phase one trial.
Dr. Lee Jones:
Exactly. So Dave is the first person I went to and said, Hey, you know, I'm thinking about this, about this study. And, uh, he, he was great. And he is like, oh, you know that. Yeah, yeah. I mean, yeah, why not mm-hmm <affirmative>. Kind of thing. And um, so once I, once I decided, okay, these are the, these are, we think we're gonna design the trial. Um, and then I'm like, we've, we've got a problem. Mm-hmm <affirmative>. We've got a problem. So, you know, if we all looking at these escalated doses, it went from, in the trial it went from 90 to 450 minutes of exercise per week. You know, think
Dr. Monty Pal:
450 minutes of exercise
Dr. Lee Jones:
Yeah.
Dr. Monty Pal:
Per week. Yeah. Wow. Okay. It's sedentary individuals doing the math in my head. So that's about an hour or so a day-ish. Yep. Yep. Hour and change. Okay.
Dr. Lee Jones:
So I thought, well, we've got a problem.
Dr. Monty Pal:
Right?
Dr. Lee Jones:
So think about the classic model in which we would do these studies. We were bringing people into our fitness facility. We had a very nice fit fitness facility on the upper side of Manhattan. Treadmills, glass windows, you know, really good real estate. Right. Uhhuh, <affirmative>. Um, and I'm like, so what we're gonna have to do, we're gonna have men who live close enough that they can come in five days a week. 'cause you know, we're not doing now just three days a week for 30 minutes.
Speaker 4:
Right.
Dr. Lee Jones:
If we're dosing people at 200, 300, 3 75, that means they've got, they've gotta come in. Right. And so I knew that that was gonna kill it.
Dr. Monty Pal:
Okay.
Dr. Lee Jones:
That would kill the trial. It would kill our abilities to do phase one trials. Because if you look at probably 90% vol exercise interventions, our oncology and beyond, they're typically fi 12 to 15 weeks, three days a week for 45 minutes a time. Right. The, the exercise intervention is typically the same in every single exercise trial.
Dr. Monty Pal:
Right.
Dr. Lee Jones:
So why is that?
Dr. Monty Pal:
I'm not sure.
Dr. Lee Jones:
So is that because we believe that's the optimal dose that has the effect on, you know, fitness and quality of life? Well, I don't, I don't think that's the case. I think it's the case. 'cause that's what research believe that participants will be willing to do.
Dr. Monty Pal:
Okay.
Dr. Lee Jones:
If you extend it longer than that, patients will drop out.
Dr. Monty Pal:
Okay.
Dr. Lee Jones:
If you say we want to train you five days a week, patients won't enroll in the first place.
Dr. Monty Pal:
And it has nothing to do with establishing a behavior. Does it? I mean, they won't carry on with this program beyond that necessarily.
Dr. Lee Jones:
Yeah. I think it's from, you know, if you're thinking about efficacy based studies, you know, we're, we're, it's not as though we're not interested what happens after the after trial. But, you know, you're testing, you want to deliver exercise at high fidelity because you want to test the, the effect of dose on outcome B. Right? Yeah. So you want to deliver that at high compliance.
Dr. Monty Pal:
Okay.
Dr. Lee Jones:
So this is why we use a supervised setting, because we could bring people in and we could watch them exercise.
Dr. Monty Pal:
I see.
Dr. Lee Jones:
Versus using an approach where they go home or the exercise at home and you don't know what they're doing.
Dr. Monty Pal:
Right.
Dr. Lee Jones:
So they might report that they're doing something, but you actually don't know.
Dr. Monty Pal:
Sure.
Dr. Lee Jones:
Um, and the other problem with that is what if, you know, something happens during the session, you wouldn't know anything about it until after the fact.
Speaker 4:
Mm. Okay.
Dr. Lee Jones:
We found that when we, you know, we are doing real time dose modifications because blood pressure's too high, heart rate's too high. So we want, we want to intervene on the spot that to us is an event. And so we would, you know, so we can precisely quantify exactly what the individual did. We know what we want them to do, but we know exactly what they did. So then we can calculate RDI
Dr. Monty Pal:
Okay.
Dr. Lee Jones:
For each exercise session. So knowing that this, the classic supervisor approach wasn't gonna work, I'm like, we need to develop a completely new way to think about this. So I thought about, well, maybe we could partner with gyms in areas and, you know, but then I'm like, that's, that's just not gonna work. Mm-hmm <affirmative>. Because one, I don't really want our participants going to this gym. You know, there can be incredibly intimidating plus how I'm gonna staff that. I've gotta have a, a staff member in every single gym. Yeah. This has gotta be covered from seven in the morning till seven at night. Like, we're gonna be bankrupt. So, so I was just, I think I was running in Central Park just thinking about this a lot. I'm like, well, I think the only way that we can do this, 'cause the idea is how do you maximize, um, the fidelity of the intervention, but also trying to maximize patient convenience.
Speaker 4:
Right.
Dr. Lee Jones:
Right. Where does, where does that meet? And so I felt that the only way we're gonna do this is if we ship treadmills to the patient's house.
Dr. Monty Pal:
So this is, this is actually where it gets pretty wild, in my opinion. This is just such an interesting, innovative concept. I, you gotta tell us how that worked out.
Dr. Lee Jones:
It took a while. So this is, this is pre COVID, uhhuh
Dr. Monty Pal:
<affirmative>.
Dr. Lee Jones:
So I thought, well, this is, this is what we need to do. So we need to need to get these treadmills to the, to these patients' houses. And you know, that's step one. So we need to partner with a company that's gonna be willing to do that.
Speaker 3:
Mm-hmm <affirmative>.
Dr. Lee Jones:
You know, white glove service, deliver the treadmill, set it up, but also then extract the treadmill.
Dr. Monty Pal:
Yeah.
Dr. Lee Jones:
Um,
Dr. Monty Pal:
I have to confess, I've had exercise machines in boxes in my house for a long time, so that that white glove service makes a lot of sense.
Dr. Lee Jones:
Yeah. A a lot of people do. Yeah. Um, and so, so that was kind of step one. So we then we had to find a treadmill that we did wasn't too big, but also if you put an iPad on it, it didn't shake too much.
Speaker 3:
Okay.
Dr. Lee Jones:
It was at the right angle. So literally we were going down to soho to, I'm not making this up. My team and I went down to soho and we're going to all these different places like commercial vendors, techno, gym, and others to actually go on the treadmill and like test these out. So we put an iPad on there and I'd run on it and we'd, we'd do all this to, and this again, this is before Zoom was a thing.
Dr. Monty Pal:
Okay.
Dr. Lee Jones:
So, so eventually, so we, I think, well, okay, we've got this to work. We had to get it of course through I-R-B-I-R-B, MSK were great. They're like, okay. I mean, sure.
Dr. Monty Pal:
<laugh>, I love it. Yeah.
Dr. Lee Jones:
So we bought, I think, I think we purchased 10 treadmills, uh, just to give this a go. And, you know, some of my staff lived in New Jersey, so we shipped a treadmill to their house and, you know, first make sure that the connection was solid and it worked out. Yeah. So we, we got that piece, we got that piece going. This is before the trial launched, of course. So we were beta testing, and then I'm like, wait a second, if, if we've got an iPad on these individuals and we're watching what, what other devices could we also send these to these individuals to now track other things that might be going on? So once I started thinking like that, like, oh, okay, this is, this is gonna be phenomenal. So we ended up, you know, thinking about, okay, getting a smartwatch to 'em. Now we can track heart rate every five minutes. We can track their sleep, we can track their mobility. We, we sent them a scale so we can get body composition every day. We, I'm like, okay, we can get 'em a glucose monitor. So we put a glucose monitor on the back of the arm.
Dr. Monty Pal:
Okay.
Dr. Lee Jones:
So we can, now I'm like, oh, that's a, now we a biomarker. It's a readout that we're getting obviously blood pressure every day as well. And so what I started thinking about is, yes, we're testing exercise, but now we're also able to collect all this other lifestyle related information. That's, 'cause we, we know what they're doing for that hour that they're with us exercising, but what's going on for the other 23 hours?
Speaker 4:
Yeah.
Dr. Lee Jones:
You know, if they're now exercising, left, moving less, that's gonna impact the trial if they're eating differently, you know, these are all the, the confounders that we have in all trials, but we never, we never measure them.
Speaker 4:
Right.
Dr. Lee Jones:
So I thought this was an opportunity, now we can go all in and start collecting all this data. And then the next level of that was, okay, well if, if that's now doing this digitized, decentralized pro, the entire trial should be digi digitized. No paper, no nothing. Everything should be electronic. The way we contact the physicians to get referrals way we consent individual, even think about consent, you bring people in, you know, you go through a three hour consent. I'm like, why are we doing that?
Speaker 4:
Yeah,
Dr. Lee Jones:
We can do that remotely. So we were the first group at MSK to do remote realtime e-consent.
Dr. Monty Pal:
So this is what sold me. I have to say, when I, when I read through all of your papers and the way that you structured these studies, I thought to myself that, gosh, with this massive transformation that we're having here, right? I was used to the model of trying to do only studies that I could do in my own backyard, 2030 patients, folks that I was seeing myself here at the institution. Now we've got Chicago and Atlanta, and Phoenix and Irvine, and all these other massive centers that are built around us. The model that you have here, I think applies perfectly to the type of study that we could do across all those centers. Don't you think?
Dr. Lee Jones:
Ab Absolutely. Um, you know, we, when we, when we had our site based approach at MSK, we would only recruit individuals who live within an eight mile radius of MSK.
Dr. Monty Pal:
Okay.
Dr. Lee Jones:
Because that we, like, if we ask individuals who live beyond that to come in, into Manhattan, you know, 65, 70% of individuals at MSK don't live in the city. They live in the, in the, in the tri-state area. So, you know, if you look at even with that, so we were losing, before the study even started, we're losing 50% of potential eligible individuals. Right. Because we didn't even consider them.
Speaker 4:
Right.
Dr. Lee Jones:
And then even with an eight mile radius, people were saying we were losing 30% of those. 'cause they said, well, it's too inconvenient and it's too far to travel. So once we, now we had this approach, this was decentralized. I'm like, the sky's limit.
Speaker 3:
Yeah. Like
Dr. Lee Jones:
We, we, we kept it with, you know, I think, I don't know what the status maybe MSK doesn't want, but basically most individuals, atm, Ms. K within a hundred mile radius. So that's where we started. Okay. A hundred mile radius. But now we're up to like 350. I mean, now coming here, particularly with multiple sites across the country,
Speaker 4:
Right?
Dr. Lee Jones:
I mean, we've all already been thinking about things in Brazil, right? So I think the sky's the limit. I mean, with this approach, there's, there's no reason we couldn't recruit an individual from anywhere.
Dr. Monty Pal:
I love it. I'm gonna shift gears a little bit now and maybe sort of ask about the, the future scape here at City of Hope. Uh, you know, I, I think that obviously you've got a ton of brilliant ideas. Where, where do you imagine your first couple of steps, um, after joining our faculty?
Dr. Lee Jones:
First of all, it's this, I'm so excited to, to be here. Um, I think when we've, we've, we first met, you were saying this was a, a bit of a hidden gem, but then you said not so hidden anymore.
Dr. Monty Pal:
Not so hidden anymore. Exactly.
Dr. Lee Jones:
Yeah. Yeah. And I think, I think that's, that's, that was spot on. And, um, you know, just the energy here in the, I, you know, I get just the people, just the can-do spirit. I just, you know, for me it was just, I just knew this in my gut. Again, it was, it was a, if it was a place to be. So we've, we've got some things to take care of initially, which is some of our legacy studies that we're bringing over from MSK. We've got three of those that we're, we're finishing off these. We've got, um, building on from, uh, localized phase one prostate study. We've got a phase two, a study in active surveillance right now with a, with a, basically a disease progression primary endpoint. So that's now, you know, taking the recommended phase two dose that we identified in the phase one. Now it's testing that in the active surveillance setting.
Dr. Monty Pal:
Okay.
Dr. Lee Jones:
Over a longer period of time, but now on disease progression.
Dr. Monty Pal:
Got it. Okay.
Dr. Lee Jones:
So that's been the, the progression, if you will, of that study. So that study's ongoing. That's an R one. It's a, it's a phase two randomized trial. We need 102 participants. I think we're at like 50 or something like that, so. Got it. It's going well. So we've gotta get that going. We've got another study in the, in the adjuvant setting where we are using, it took, this was a phase one, a phase one B trial. So phase one, a dose finding in the adjuvant setting, looking at both compliance or feasibility, as well as things like peripheral immune response as well as C ctdna.
Dr. Monty Pal:
Mm-hmm <affirmative>.
Dr. Lee Jones:
We finished the phase one A, the dose finding. Now we're doing the phase one B dose expansion.
Dr. Monty Pal:
And just to clarify, what setting is that? That's in? Uh, this
Dr. Lee Jones:
Is all in individuals. Initially it was in we breast and colon, but
Dr. Monty Pal:
We've,
Dr. Lee Jones:
In the phase one B, I want to extend it to any solid tumor post.
Dr. Monty Pal:
Great. Okay.
Dr. Lee Jones:
Post definitive therapy.
Dr. Monty Pal:
Got it. Got it.
Dr. Lee Jones:
And that's, uh, you know, initially that's a six month intervention.
Dr. Monty Pal:
Mm-hmm <affirmative>.
Dr. Lee Jones:
Again, all decentralized. Um, well, individuals have the option to continue exercising for another 12 months. So it's a potentially 18 month individual intervention, um, with serial blood collection. And again, our blood collection is all done remotely as well. So individuals don't need to come in.
Dr. Monty Pal:
Amazing.
Dr. Lee Jones:
To do that blood collection. Wow. So we'll do the same thing here. It's City of Hope. Um, so we, there, there are two big studies that we, that we, that we want to go in. Um, and then after that, you know, I think we've, I've got four R ones that are in, in the works, so
Dr. Monty Pal:
To speak. Oh my gosh. Okay.
Dr. Lee Jones:
You know, at various stages. Ones that we've got a big study in Lynch.
Speaker 4:
Okay. So
Dr. Lee Jones:
We just finished this Lynch pilot. So we're very interested in interception, in high risk in individuals in the prevention setting. Lynch is a, is a, I think a great setting for that. We just finished with 30 15 individuals a year of training. We got tissue pre-imposed. We're doing, you know, single cell RN AE on it, as well as the pbmc is doing single cell and that to look at immune infiltration into, into the tissue. I think we've got some really interesting data there. So now I want to do the next study again. Now a phase two, A powered on events.
Dr. Monty Pal:
Okay.
Dr. Lee Jones:
So that's that. We also just finished a study in high risk, uh, women for breast cancer. So these are BRCA one, BRCA one, BRCA two, high family history. We just, uh, I think we just, again, we did a dose finding study, actually we did a co clinical trial dose finding in individuals at high risk. Then we did the mouse mirror image study. Interesting.
Speaker 4:
Okay.
Dr. Lee Jones:
Same exercise doses, same duration of exercise.
Speaker 4:
Okay.
Dr. Lee Jones:
For, to, to identify the recommended phase two dose. I think we did that. Um, so now we want to do again the phase two A study, which will be a randomized study. So we've got that one in the works. Um, and then we, we have a couple of other studies. Um, I think we've got one in breast. Um, so the idea is now is, you know, let's, let's, let's see where, how they do, see how they score, see if we need to put 'em back in. These are all multicenter studies.
Speaker 3:
Mm-hmm <affirmative>.
Dr. Lee Jones:
Um, so they're kind of, you know, we've got these legacy studies. We've gotta get the IOB approval. We've got these R ones that I want to get in and get done. We've, um, we're writing a grant right now actually that will be in basically triple negative breast cancer, getting neoadjuvant chemoimmunotherapy. And we're looking to do that study within
Dr. Monty Pal:
Ipy. Okay. Oh, great. With with Hope Rugo joining us. Right. With, with Hope. Exactly. Absolutely. Oh,
Dr. Lee Jones:
Terrific. Exactly. So that's, that's the idea there. Um, so we're working on that. And then after that, quite honestly, what, what I would like to do is be a
Dr. Monty Pal:
Sponge. Okay.
Dr. Lee Jones:
I want to meet with you more often. I want to come to all the rounds. I want to, I want to come to as many research meetings as possible. Um, and just, I just want to, yeah, I want to be a sponge. I want to take it in and, and I think just, just learn what people are doing here. Um, and I think that's, that's, that's then gonna generate I think, new ideas and rather me coming in and say, what, you know, my path is set. This is what I'm, you know, I've got that. But I think the, the amazing opportunity here is to come into an environment, learn what people are doing, innovative approaches, and then see how our work fits into that. Or, you know, it makes us think differently. I mean, again, that's, that to me is the opportunity. This is why I've come here, is not for me just to do the things that I was gonna keep doing at MSK is to do something different, right. And really blow it up. And I think, you know, the, the infrastructure that City of Hope has really, I think, blends very well with, with the approach that we have. And so just imagine the studies that we could, I wanna, I want to like dream big. I wouldn't dream big.
Dr. Monty Pal:
It's so funny because oftentimes you hear about people transitioning institutions and occasionally, you know, they're very appropriate. They'll take a couple of months off, relax, travel the world and so forth. But what I love about you is that I don't think a week or two has gone by when we have an exchange, an email or a thought, you know, around what you know you're doing and what I'm doing and so forth. And, you know, clearly from our discussion now you've engaged with Hope Rugo, our, you know, sort of internationally acclaimed breast cancer expert you're incorporating in her trial ipy. This is just all fantastic. And we are just so absolutely excited about the possibilities that emerge from having you here.
Dr. Lee Jones:
Yeah. I I, I'm so excited. I think, um, you know, I, what, the way I look at it is we've, we've now got this foundation
Speaker 3:
Mm-hmm <affirmative>.
Dr. Lee Jones:
And now we can, we can, you know, the infrastructure, the foundation, some initial data to really go to the, to the next level.
Speaker 4:
Yeah.
Dr. Lee Jones:
And then some, so yeah, the sky's the limit. I, I can't wait to get going. I mean, this is the first week and it already, it's been phenomenal. And, um, yeah. You know, build a team, get to know people and do things that people don't, you know, would I want people to look at, you know, look at the trials and be like, you guys are doing that? I, you know, that. I love it. That kind of, that kind of
Dr. Monty Pal:
Response. You know, what we should do, Lee, is let's, let's remember this moment and five years from now, let's do the same podcast together, <laugh>, and see how much of this has come to fruition. I, I have a feeling a lot Will. So I, I'm super excited about that. You know, one of the things that we always sort of close the program by doing is asking our guests a question. And, and this is a tough one. Uh, the title of our podcast is On the Edge of Breakthrough Voices of Cancer Research. What does on the edge of breakthrough mean to you, Lee Jones?
Dr. Lee Jones:
Yeah, I think it's, it is a great question, and it, it is a tough one. Um, I think we're always on the edge of breakthrough. I think we're on the edge of breakthrough all the time. We, you know, it's, there's not a finished post, right? Um, it's not as if we will do a trial and say, that's it, we're done. You know, there's always, this is why I love science so much, is because there's always something else. There's always something that we always can do better. Um, I guess what I'm really excited about is, is I think there's a paradigm shift coming in, in oncology, um, in really recognizing the, the interaction between the environment, who the person's physiology, who physiology, the tumor microenvironment, and of course, um, the cancer cell itself. And I, you know, I think, so for so long we've been focused on the cancer cell, and of course we've moved now to the tumor microenvironment.
But I think now this next level of starting incorporating, um, you know, cancer doesn't exist in a vacuum, right? It's, it's, it's surrounded by this host that, that feeds every cell in the body, including cancer cells. So these holistic level interventions and how that blends with an individual's environment, I think that's where we, that's where we need to go. And it's, it's, it's been very, I think, um, it's been amazing to see some of these, some of this coming out now, some of these being some big reviews. I think there's one in cell, there's one in nature medicine starting to talk about on, on this kind of level. And so think about the opportunities at that level, the, the types of data that we now need to collect that we've, we've ignored
Speaker 4:
Yeah.
Dr. Lee Jones:
Before that we know has such a profound impact on the way that individuals respond, uh, to therapies already, how they might even develop cancer in the first place. So yeah, I'm excited about that because I think that's the way, you know, that's, that's biology, that's physiology. Um, but of course, the things that I do fit, I think fits very nicely into that. So I'm a little bit biased, but I think the opportunities that, that creates for us to think differently, the types of data we need to collect and how that's, you know, I think it really is now, it is a more patient centric approach. Um, and so the opportunities in, in the discoveries that we, that we're gonna make as and others, I think, um, over the next decade are just gonna be remarkable. It's gonna be remarkable. So I'm very excited about that. So that's the next edge of discovery, you know? Yeah. That's happening all the time. Every day I go into pub, right, there's a new discovery, like, oh, that's so cool. That's so cool. And so this is happening all the time. Um, so that's what edge of discovery means to me.
Dr. Monty Pal:
Brilliant. Brilliant. You, you know, it's so funny, folks ask me, what is the most common question you get in the clinic? It, it's actually not, doc, what drug should I get? Right. It, it's, it's never, you know, the things you might anticipate, you know, how long will I live? You know, these are common questions you would imagine would arise in an oncology clinic, but rather, folks always ask first and foremost, what should I be eating? The second question that always comes to mind is, what else can I do to enhance my health? And exercise is always a part of that equation. So we are very, very lucky to have you here to help really sort of get at the root of the questions that all of our patients are asking. We thanks so much for being here.
Dr. Lee Jones:
Yeah, it's my pleasure. And I'll just finish on that. I, I really see it as my job is to put that data into your hands to inform those kind of discussions. Um, because that's, that's what we need to, and I, I think, you know, we're getting there, but we've, we've got a long way to go. But, um, I agree. I think, you know, individuals are always very interested in what they can do to impact their own trajectories and, uh, yeah. Yeah. And I see, see, it, my job is, is proving and providing the information to inform those conversations.
Dr. Monty Pal:
Okay. Five years from now, same time, same place. Okay,
Dr. Lee Jones:
You're on.
Dr. Monty Pal:
Alright, <laugh>, let's see you then.
Dr. Lee Jones:
Okay. Thanks so much.