ERASur trial: Local treatment options for limited stage IV CRC

Manju George 00:00
Hello, everyone. Welcome to Doc Talks. I’m Doctor Manju George, the scientific director at Paltown Development Foundation, the nonprofit that supports Colontown. Today, we have the privilege of having the principal investigators of the ERASur trial with us to tell us about their trial. So I will turn this over to the panel. Dr. Miller, do you want to introduce yourself?

Dr. Eric Miller 00:26
Thanks, Dr. George, I’m Eric Miller, I’m one of the radiation oncologists at Ohio State University.

Manju George 00:32
Dr. Hitchcock?

Dr. Kathryn Hitchcock 00:34
Thank you, Dr. George, thank you so much for having us here today. My name is Kate Hitchcock. I’m a radiation oncologist like Dr. Miller is, and I practice down here at the University of Florida, Go Gators.

Manju George 00:46
Thank you very much for joining us. So we can get started. I think Dr. Romesser is in clinic. So he’ll be joining anytime soon. So let’s get started so we don’t waste any time.

Dr. Kathryn Hitchcock 00:56
That sounds like a great plan. I’m hoping that we will get a lot of good questions at the end here. So we’ve intentionally written our talk to leave lots of time for good discussion in case folks are inclined toward that. So I’m going to start us off here, and the first thing I’m going to do, Eric, if you don’t mind flip into the next slide, is talk about what it is that we’re treating here. This study, the research study is designed to treat all oligo metastatic colorectal cancer. Oligo metastatic is a word that came about not too long ago, to describe a situation where a patient does have metastases from their cancer, but there’s only a few of them. And that’s what that word oligo means it’s from the Greek word meaning just a few or little. And the reason we needed a word for that, and the reason it was a new word is that up until you know not that long ago, 10 or 15 years ago, people really believed that if you had any metastasis anywhere in your body, that it was a signal that the cancer had spread to all of the parts of your body and that the cancer was there for incurable. We know now that in many, many cases, that is not true that there is a state in many cancers where yes, the cancer has metastasized to a new place. But if we are really careful and a little bit aggressive in treating that one place, or a few places that we can still cure the cancer, and colon and rectal cancers are definitely the prime example of this, I would say that this is the disease that people always think of first, when they think of curing folks with oligo metastatic disease.

And so some smart and brave people started really trying to cure the patient in that situation that started out with resecting metastases in the lungs that were because they were easy to see even when our imaging was not so good. And you can see we’ve given you some references there, we’re showing where people were resecting metastases from sarcomas and also from colorectal cancer. The liver then was the next one after MRI became common, and it was easy to find liver metastases, people started resecting those and the reason the liver and the lung were the places we started is that you can live without quite a bit of those two organs, you’ve got a lot more capacity for lung than you really need. So if somebody needs to take some out, you’re still going to do well afterwards and not have breathing problems.

You might know that your liver is one of the few parts of our body that grows back completely. That’s why we can donate part of our liver to someone else. And that part of the liver that’s taken out regrows. So if we do a surgical resection on part of the liver, it’s okay, you’re going to be fine with the liver that’s leftover if it’s done skillfully. And then that part of the liver will regrow. So that’s how things got started.

And ready for the next slide, Eric.

So we have some really, really good technologies now that give us lots of different tools to try to address these oligo metastases. As I explained, this started out with surgery, but there’s places where you can’t do surgery or maybe the patient just doesn’t want surgery to their body and all of the effects that that has. With the other options that we have our SBRT (stereotactic body radiation therapy), which means very intense, very focused radiation therapy to kill metastases. There’s also ablation that can be done in a lot of different ways. You see that in the middle panel on this slide that involves putting a probe into usually the liver in order to kill a metastasis or multiple metastases there. And of course, we still can do surgical resection. And it’s not uncommon for patients to need a combination of two or more of these techniques to address all of their sites of metastasis.

I’m so happy to be alive in a time in which we’ve started to really accumulate lots of data that shows that those techniques that I just described, you really do help. And we’ve shown you some panels from a couple of different studies here, showing that if you do go after liver disease here in the leftmost graph, or lung only disease over here on the right, this is patients who had metastases in their liver that was unresectable. And so they were being treated with a combination of surgery for the resectable ones, and that ablation technique for the ones that weren’t resectable.

And I think you can see here, if you look at these graphs, that there is a big difference in what happened to patients who got that intense local therapy, and those who didn’t, you don’t have to be a statistician to see that those two lines are not on top of each other. And what that means is, when they went after these oligo metastases, and really treated them aggressively, it helped patients a lot. Even though, let’s see, these studies were published in 2017. So you got to figure they started probably writing the studies in about 2007. And even, you know, five or six years before that, it would have been very difficult to convince anyone to go after these metastases with surgery or anything else. So this was a big revolution in the way that we treat cancer. This was a very, very big deal.

All right, I’m ready for the next slide, Eric, thank you. So the beautiful thing that’s happened even more recently is that we’ve been able to show that SBRT that intense radiotherapy also does an excellent job of treating oligo metastases. And it has been doing that for a long time, we’ve been using SBRT in this way for a long, long time. Now, unfortunately, there’s lots of radio phobia out there in the world, even among very educated people, like physicians. And so it’s been harder for people to accept using radiation treatment, like it often is. But it’s a great tool, because it’s the only one of those three techniques I showed you, that doesn’t involve poking any holes in your body. It doesn’t involve any blood loss or risk of infection. And my patients, when I treat them with this technique for oligo metastases do very, very well, it’s extremely uncommon for them to have really any side effect other than fatigue. So it’s exciting these graphs that you see here showing that when we use SBRT to treat oligo metastases, we get those same excellent results that you saw on the previous slide, for surgical resection and for ablation, and that’s what the study that we’re going to talk to you is all about. And then I hand it off to Eric, I think are you the middle slides here?

Dr. Eric Miller 08:08
Yep. Thanks, Dr. Hitchcock. So as Dr. Hitchcock really still skillfully described, we know the standard of care for patients who have a liver metastasis. If you remove that liver metastasis, either with surgery or with another ablative technique, we know that those patients do very well. And even a subset of those patients can be cured, so it can go a long period of time before any other type of cancer shows up anywhere else. So we know that there’s a benefit to local therapy in this patient with the liver metastasis. Our question is, what if a patient has a little bit more metastatic disease? What if they have two lung metastases in the liver metastasis and a lymph node metastasis? What is the role of local therapies such as radiation and ablation and surgery for that type of patient? And, really want to answer the question of why do we need a trial in this space? So right now, to date, there has not been a study looking at the use of multi modality and when I say multi modality, I mean, the use of radiation or ablation or surgery for metastatic directed therapy for colorectal cancer, and it really has not been done to date in a systematic manner. And the reason why it’s important is that, as Dr. Hitchcock described, imaging is improving, we have better techniques to find cancer and to detect cancer, we have better therapies to treat cancer. And so the use of that type of therapy outside of studies is rapidly expanding. And rather than it being really evidence based, there’s really no science behind treating that type of distribution of disease. It’s really provider bias rather than evidence-based and we all know that you really want evidence to prescribe a treatment. And so the benefit of extending the treatment paradigm that we have for patients with liver-only disease, where we know there’s a benefit, the existing paradigm for patients with more extensive disease is currently undefined. And you really have to balance it with any potential toxicity from the treatment. And so our trial ERASur is really hoping to fill this knowledge gap. And we’re designing what we think is a practical multimodality approach that mirrors the current clinical dilemma that we’re in.

And so this is our study. It’s a pragmatic randomized phase three trial, evaluating total ablative therapy for patients with limited metastatic colorectal cancer, evaluating radiation ablation and surgery. It’s called the ERASur trial. And it’s a joint trial between Alliance and NRG oncology, two different cooperative groups, national cooperative groups focused on on developing better cancer therapies. And we’ve really assembled a really great group of individuals with a lot of talent and expertise in different disciplines to help answer this question and conduct this trial.

So the primary objective of a ERASur is to evaluate and compare survival in patients with newly diagnosed all oligo metastatic colorectal cancer treated with total ablative therapy. And what we mean by total ablative therapy is treatment of all sites of disease using radiation, with or without surgery, and with or without ablative therapy with heat, adding that to chemotherapy versus just chemotherapy alone.
Number of secondary objectives for the trial as well, including looking at event free survival. So progression of the cancer, looking at safety of the treatment, as well as time to local recurrence meaning return of the cancer where it was where the individual local therapy was delivered, so a local recurrence of the cancer.

So this is the design of this study. So it’s including patients with newly diagnosed limited metastatic colorectal cancer and Dr. Romesser is going to talk about what we’re defining as a site of disease, but it’s for fewer sites of disease. On the initial baseline imaging that includes CT scans, the primary tumor, so the colon or rectal primary tumor must be either already removed or able to be removed, BRAF wild type or microsatellite stable disease. Patients can’t have liver only disease because we really, we know the paradigm for that already exists. But surgical resection or local therapy is beneficial in that patient population. So patients receive systemic therapy for four to six months. Those who progress on first-line chemotherapy are removed from the protocol because we know those patients should consider alternative therapy. And then patients who do have residual disease, meaning that there is still disease visible on subsequent CT scans. Following induction systemic therapies, that four to six month period of systemic therapy, patients have been randomized to continue standard care, systemic therapy, or the addition of total ablative therapy. And that, again, is ablative of radiation with or without surgery, and then with or without microwave ablation. And the primary endpoint of this study is overall survival. So I’m going to turn it over to Dr.Romesser to talk about the eligibility criteria.

Dr. Paul Romesser 12:54
Good afternoon, everyone. I hope everyone’s having a nice day. Thank you for joining us. So thank you, Dr. Hitchcock and Dr. Miller. So when we’re thinking about eligibility criteria for this study, we definitely want to limit it to metastatic colorectal cancer patients who are not known to have microsatellite unstable tumors, because those are patients who would likely benefit from a different type of therapy, largely immunotherapy.

We don’t want them to have known BRAF mutations where they might benefit from the BRAF inhibitors. No known peritoneal or omental metastases just because that’s not something that we can treat from a localized perspective. That takes a different type of treatment. And the primary tumor, the primary colon or rectal tumor needs to either have been surgically resected or amenable, to resection as part of this paradigm meaning that we have to address not only metastatic disease, but any localized or primary disease as well.

Patients can have up to four or fewer sites of metastatic disease, and we’ll talk about what a site is, but liver-only diseases not permitted largely because the studies that Dr. Hitchcock showed at the beginning have really reported on excellent outcomes where a subset of patients can have very prolonged progression-free and overall survival, are essentially cures as we see them. And so we don’t think we need to reestablish the you know, the wheelhouse there.

And then patients can have a maximum of four months of systemic therapy. So for registration, the patients can have any progression on induction chemotherapy, they can’t be eligible for hepatic arterial infusion pumps, which are gaining momentum and traction around the country. They must have measurable disease on imaging. And again, a minimum of four months of systemic but maximum of six months so really have to come in right in that sweet spot for eligibility.

And if they had prior definitive or curative intent treatment like such as stage two or stage three disease, they must be greater than 12 months out or greater than 12 months out from completing that, that treatment. No pregnant patients and everyone must be older than the age of 18 with a good performance status and labs as shown here.

Sorry, my eyes watering. So what’s a metastatic site? So it’s interesting, it’s, it needs to be radiographically evident, you know, biopsy or pathological confirmation is not required, but the patient does need to have a diagnosis of metastatic colorectal cancer, then lesions must be amenable to any combination of surgery, microwave ablation, which is the interventional radiology technique and or stereotactic body radiotherapy. Which is SBRT or stereotactic ablative radiotherapy, which is saber, they mean essentially the same thing.

So what’s a single site? Well, each side of the liver, we have a right and left side of our liver. So that’s the right side would be one site, the left side would be another site. Each lobe of the lungs is a site. So in the right lung, we have three lobes and the left lung, we have two lobes, and different organs like each adrenal gland with two adrenal glands on either side of her body, and those would be considered each of them a single site. Lymph nodes are a little bit harder to define, because lymph nodes obviously can be next to each other or spread out. But if the lymph nodes are amenable to single surgical resection, or can be treated in a single saber radiation field that would compromise a single site and bone metastases amenable to treatment in a single saber field by a single site, and we left it intentionally not overly restrictive, or, or, you know, confining, to allow us the flexibility of the sites of the of the centers, or the doctors to kind of have flexibility and kind of determining, you know, who is a good patient and to what level can we can we enroll them at.

So their study interventions, the control arm, you know, it is a randomized study. So patients will be randomized to either control or the experimental arm, the control arm is going to be continuing the standard of care chemotherapy. We allow maintenance chemotherapy, as well as local metastatic directed therapy for patients who have, you know, pain, discomfort or need palliation.

But for lesions that are not not causing any symptoms, we don’t allow local therapy. And that’s really kind of the standard. On the experimental arm, we give up to three months, to essentially complete what we call total ablative therapy, which is again, surgical resection, microwave ablation, or saber to all sites of disease. And thereafter, we ask the physicians to reconsider starting chemotherapy, as is. Again, chemotherapy breaks on both arms are permitted at the discretion of the primary team and this often do occur in the real world. And so it’s meant to be somewhat pragmatic in terms of mirroring what’s happening in the real world setting. But really looking at the addition of TAT or the total ablative therapy in this cohort.

For correlative study perspective, we’ll be asking patients to agree to allow us to bank their blood for future CT DNA studies. And I want to point out, you know, one thing that Dr. Hitchcock Dr. Miller and I were really, I guess, proud about and enthusiastic about, you know, we approached Dr. George, who you all know, early on and said, We’re designing this trial, but it’s important for us to hear from patients, it’s important for us to get the patient input. We wanted to know, a) was this something that they’re interested in was this enthusiasm. And also, we ask very pointed questions about what would they prefer? And in what order and to what degree they thought, you know, we should let patients enroll and what sorts of different types of treatments they would would agree to. And so the the patient perspective and the patient input for this trial was absolutely critical.

And it’s critical from an early early development time point. So I want to thank Dr. George, the entire COLONTOWN family and Paltown on behalf of all of us in terms of helping us with the trial design, and I think that’s really something that I know that we’re all very proud of. Separately, I just want to point out that your input helped us get this trial through and approved. 90% of you responded and said you would consider enrolling on this trial. 70% of you were enthusiastic for a potential treatment break. In terms of considering maybe omitting maintenance chemotherapy, in the setting of using maybe ctDNA analysis. Unfortunately, the National Cancer Institute and the GI steering committee felt like that was pushing the envelope a little bit too much, and they kind of dialed it back. But that’s something we’re going to look at in the correlative studies, and something we’re gonna consider for future studies down the road. And having something like this, where we’re showing 90%, enthusiasm, 70% enthusiasm, this is unparalleled. And I just want to really highlight that this made a really big deal. And it was incredibly impactful when we brought this to the National Cancer Institute, in terms of showing feasibility, enthusiasm, and overall, you know need for the trial. So thank you very much. So with that, I want to invite Dr. Hitchcock and Dr. Miller to kind of chime in here as well. And just really wanted to say we want to answer your questions. We want to bring up, highlight the trial. But we wanted to come here to thank you, most importantly, for your input with the trial design, and we hope they will continue to support us and guide us as we lead this trial for next couple years. Dr. Miller, Dr. Hitchcock,

Dr. Kathryn Hitchcock 21:44
I think we started to get some questions here in the chat. So if it’s alright with you, Dr. George, I’ll start working our way down the list here.

One question, when do you expect the sites to start recruiting? The study is officially open. And there are sites all over the country right now that are working on getting it open, you would be appalled if you saw how much paperwork it takes just to make it possible to treat somebody on a study like this. So I think everybody everywhere right now is in the process of getting this through the Institutional Review Board where they are, meaning the people who take a look at studies to make sure that they’re going to be done ethically and are going to respect the the rights of the patients who might be treated on this study. And the minute that’s approved, we’re ready for action, we’re so enthusiastic to start getting patients on the treatment on this trial.

Manju George 22:45
Dr. Hitchcock, I was kind of wondering that, since the video will be posted and this trial is now in the feature trial sections on COLONTOWN University, it would be kind of nice to know, you know, if you if someone can give us a list of what places they’re open, we will be happy to put it up on the website. So that I think this is a question that we often get from patients like they want to know where it’s open so they can talk about it. So that’d be nice to know, like as you get information on, you know, where all it is open?

Dr. Kathryn Hitchcock 23:16
That sounds like a great idea. And I think probably the smart thing would be I think there will be the Alliance cancer research group is the lead on this. Probably we can find a link to their page that it shows which sites are open, we’d be happy to pass that over so we can drop that into the site.

Manju George
Yes, that’d be great.

Dr. Paul Romesser 23:39
Yeah, is probably the day. So having a site I think would be critical. So Dr. Miller,

Dr. Eric Miller 23:45
Thank you. So also, I think on the colon cancer website where it’s a feature trial, there’s a link to the clinical trials.gov site. And that actually will contain, once sites are open, that will contain where all it is going to be open or where it’s open right now. It takes a little bit, a couple of months for it to actually get open. So we’re getting closer.

Manju George 24:08
Okay. I think there’s a question about the sites.

Dr. Eric Miller 24:12
There was a question about this four or fewer sites mean, you could have more than four spots, and that’s as long as they were confined to less than four sites.

That’s exactly right. That’s how you interpret it. So you can have, for example, in the right upper lobe of the lung, you can have two or three individual mets or lesions there. And that would be considered as one site. So that is under percent correct.

Manju George 24:35
For the patient that had a recurrence after curative intent liver resection be eligible?

Dr. Kathryn Hitchcock 24:40
Yes, they would. There’s a time limit a certain amount of time has to pass between that curative attempt and being treated here but it would definitely be worth looking into this study in that situation.

Manju George 24:55
I think the next question is about somebody from New Zealand. Would you consider patients located outside the US?

Dr. Kathryn Hitchcock 25:04
Absolutely, yes, in the United States, it always just comes down to how the hospital is going to get paid. So as long as that end of things could be worked out, I don’t see any reason that we couldn’t treat somebody from anywhere. We would love to take care of that patient.

Manju George 25:23
Yeah. So the next question is, would the patient have to have primary resected? I’m not clear on amenable to resection. What does that mean?

Dr. Kathryn Hitchcock 25:32
So great, great question. So it either has to be resected, before they get into the trial, or in the early period of the trial, it has to be resected. So amenable to resection, means it’s possible to be resected. And the patient agrees to have their primary tumor resected. Because the question that we’re testing is in people who don’t have their primary tumors still sitting there as a source of potential new metastases.

Manju George 26:05
I was kind of wondering, could you go back a couple of slides, where you had the control arm and the experimental arm?

Dr. Eric Miller 26:12
Yeah. Which one do you want to look at?

Manju George 26:15
I think there was one where you had on the left side, you had control? Yeah, that’s the study interventions. Yeah. So I was kind of wondering, can we think of a hypothetical patient, and then kind of go through each step? how that would be so that people are really clear about, you know, how this is happening. So let’s say I’m a stage four patient, and I have, you know, a primary tumor in my colon, and then one or two mets in my liver, couple of lymph nodes in the abdomen, and then one or two spots in the lung? So do I register now? Or, like, Could you walk me through that?

Dr. Eric Miller 26:53
Yeah, I can, I can try to tackle that one. So we actually designed it so that you can register, really any anytime during that initial six month period. So you can register before you start chemotherapy. Or you can register and that would be called pre-registration. Or you can register after that four month chemotherapy period and register at that point. So you can kind of register all throughout induction chemotherapy. But essentially, you would finish at least four months of chemotherapy, you’d register to the trial. At that point, you would then, you know, make sure that you’d meet all the eligibility criteria, you know, the lab values, make sure everything else is in order. You would have restaging imaging. And the one thing that we had talked about, kind of maybe glossed over a little bit is to make sure that there’s still something to treat. So if everything disappears on that restaging imaging, that’s great. But that would mean that you may not need local therapy, and we want to make sure that we know what we’re treating. And so there needs to be something that we can actually see on the imaging to treat. And so at that point, then you would be randomized for patients who still have something there’s a lot to treat, you’d be randomized to either continue chemotherapy, or local ablative therapy or TAT plus chemotherapy. There is some time built in there where you could get additional chemotherapy if necessary. We allow up to 90 days to get the total ablative therapy done. And so you work with your primary team, if you randomize to the TAT arm, with your primary team to figure out the best combination of therapy to treat all areas of disease. If you randomized to the chemotherapy alone arm then you would continue with chemotherapy. And then after you finish that treatment, you would then follow up with routine imaging scans and blood tests as you would off of this study. Did I miss anything? Dr. Hitchcock or Dr. Romesser? Sorry.

Dr. Kathryn Hitchcock 28:53
No, I thought that was a great explanation.

Manju George 28:55
Okay, so can I ask some questions about it? So when people are getting chemo, they can get anything they can get FOLFOX plus the biologic. If some patients wanted FOLFOXIRI, they would still be able to get that too.

Dr. Kathryn Hitchcock 29:12
Right or Yeah, okay. Yeah. And then we fought really hard for that. There were folks or advisers along the way that wanted us to specify, but we wanted people to have lots of lots of options, especially since everybody’s situation is different.

Manju George 29:25
Okay, okay. That sounds good. And then so, so you get like four months of chemo. So let’s think of my case. So I got four months of chemo. And then I had imaging and, you know, one month in my liver is gone. The lymph nodes have shrunk down, I can’t find anything on my lung. So I have now mets in the liver and, you know, the lymph nodes. So which means I can still continue with the local ablative therapy, right?

Dr. Kathryn Hitchcock
That’s okay.

And then I have 90 days during which time I can get radiation to the lymph nodes. Maybe have some thing down to the liver. And then I have that much time off chemo then is that what is meant, like in that 90 day period, I can get all the local treatments done.

Dr. Kathryn Hitchcock 30:09
Exactly. Because most of the time, if you’re doing these more concentrated therapies, you don’t keep chemo going, you want to make sure the body has a chance to recuperate from what it’s been through. So you get a chemo break during that time. Exactly. Right.

Manju George 30:24
Okay. And then after that, after the 90 days, you have one imaging, is it?. Okay, okay. And then you can continue with the, you know, either maintenance. So, let’s say after the imaging, there is nothing seen on scans, and you also have blood draw for ct DNA, and then you can, so I can talk to my care team. And, you know, if all the lesions are gone, I can go back to maintenance, just get Cape Bev and continue or if I wanted to take a treatment break, would it be possible to take a treatment break too?

Dr. Kathryn Hitchcock
Absolutely, yes.

Manju George
Okay. Okay. Okay. And then you’re going to watch me to see when those lesions come back, or if I have additional lesions? That’s, that’s what you’re trying to look at ?

Dr. Kathryn Hitchcock 31:05
Correct, exactly. Okay. Okay.

Manju George 31:07
Thank you very much. This was this. This was very clear. Let’s see if there are other questions. Okay. Paula has a question. If there is a large tumor considered to be one tumor, but in both the right and left lobe of the liver, Does this qualify as two sites?

Dr. Eric Miller 31:25
Good question. Actually, we didn’t think of that scenario, but I would probably kind of just two sites.

Dr. Kathryn Hitchcock 31:30
I think the way we have it written it would probably count as two,

Dr. Eric Miller 31:35
It’ll be a judgment call, but probably too, to go back. Just one thing to add to the I think that was a great explanation. Dr. George a great thought experiment of going through the trial, but so you would have 90 days to finish TAT. And then the first imaging time point is really one month after finishing TAT. So you finish TAT, let everything kind of calm down. And then 30 days after that is the first imaging time point. And then it’s it’s every three months that you would kind of do normally. But yeah, everything else was exactly correct.

Manju George 32:09
So Betsy has a question. Could I get the slides to post deliver Lovers Lane, Langston, and Legos land? So these are called on groups for different mets?

Dr. Kathryn Hitchcock 32:21
So yeah, yeah, absolutely. Yes. Yeah.

Manju George 32:22
Thank you so much. This was very helpful, especially, you know, walking us through a scenario that was, that was really helpful. Let’s see if people have other questions. They have plenty of time. Yeah, Brain mets? Are they eligible?

Dr. Kathryn Hitchcock 32:39
Unfortunately, no, we went back and forth about this early on, and they would not let us include folks with brain metastases.

Manju George 32:50
Okay. Okay. And then I had this question about CtDNA. So are you planning certain time points like how’s that being planned?

Dr. Paul Romesser 32:59
We built in specific time points we’re working, we’re asking all the sites to draw blood for ct DNA analyses. So they’ll draw the blood, spin it down and send it to a central repository, which then we can actually go through and do the analysis after the trial is complete. So they are standardized, there’s four or five of them throughout the trial, that are pretty well standardized. So that’s something we’re hopeful that patients and sites will enthusiastically participate in.

Manju George 33:35
Okay, so the only thing like I what you explained with the GISC not thinking not allowing ctDNA testing. So if it’s going to a central facility, that means that people won’t be able to, you know, you’re probably not analyzing it during the trial, is it?

Dr. Paul Romesser 33:52
Correct or not analyze it during the trial. Now, that’s not to say that, you know, there are some centers that are routinely using ctDNA, and they may still want to continue their standard practice, others aren’t doing that in the metastatic setting. So we’re not here to, you know, opine on that or to prevent anyone from using it. But from a scientific perspective, we won’t be able to use an external ct DNA test that that site is using, but if we have a little bit of that blood bank, we can go back and with, you know, one or two vendors, go back and do the analysis for the full whole cohort. And we’re certainly very enthusiastic that it may identify or help us identify patients who would maximally benefit from these types of interventions in the future.

Manju George 34:47
Okay. Okay. So just, not to put you on the spot. But just to ask, so what when you said that if there was a site that was already using ctDNA testing for these kinds of patients, then those patients would get the results? So but the blood would be banked and that banked blood is what you will do for your analysis for the trial endpoints. Is that what you meant?

Dr. Paul Romesser 35:09
Yeah, so the bank blood is just banked. It’s not analyzed in any patients upfront. But if a doctor at Site y, for example, routinely sends ctDNA on their patients, his or her patients, he or she can still on their own accord, draw an additional tube of blood and send it for real time ctDNA analysis. Okay, that’s just not part of the trial will be included in a trial, and that’s not data that we collect on the trial.

Manju George 35:41
Okay, okay. Okay. So, sorry to belabor this, but what it means is that if the patient is in a center where they routinely use ctDNA, then they will be able to get the results of the ctDNA testing too, but if it’s not, then they won’t have the data because that data is not analyzed till the end of this trial. Right. Okay. Okay. Yeah, it’s good to know, because we didn’t want patients to be confused, you know.

Dr. Paul Romesser 36:08
Put a maybe a little bit more clearly, there’s their no ctDNA, patients will not get any ctDNA information or testing done. In real time on this trial, any ctDNA testing that they want done on the trial is outside of the trial and their provider will have to do that separate.

Dr. Kathryn Hitchcock 36:33
Okay. But with that said, they can still make decisions based on that we’ve intentionally left it. So whatever information you have with your care team, whatever decisions you are going to make, normally, we’re not stopping you from making that decision on this trial. We tried to make it as unrestrictive as we could, so that we weren’t taking any options off the table for anybody.

Manju George 36:58
Okay, that’s absolutely, yeah, I think that’s a great point. Because I think that’s where I was trying to get to that, I mean, the design is in such a way that, you know, it allows the maximum flexibility. And for every patient, wherever they’re located based on what their care team is doing, they can actually use the, you know, the tools that are available in the child, but then they have the care that is almost tailored to how they are getting it anyways. Right? Yeah. Okay. Paula has a question, how does insurance handle this trial? Can the patient remain where they live? Or would they need to be at a specific center long term?

Dr. Kathryn Hitchcock 37:35
The beautiful thing about this is, you have to be treated at a site that has the study open. So you can’t enroll in this study at one hospital and then go get your ablative treatment at another. However, you can get your chemotherapy someplace else. So we were hoping that would for patients who don’t have an enrolling hospital near them, they could come and get enrolled and get their local therapy if they were assigned to that arm and then go back home and get their chemotherapy and not be stuck anywhere for months and months getting chemotherapy. But any center that has the trial open can do the local therapies. There’s not one or two sites, we’re hoping to have, in fact, quite a few sites. So hopefully, there’ll be one close to everybody who wants it.

Manju George 38:28
Okay. Okay. Thank you very much. That’s a great point. Great question, Paula. So basically, so I will just summarize what you said. So chemo, if I’m a patient enrolling in the trial, I can get the chemo at my local wherever I get my treatment, but I have to enroll at a place where I will get the local therapies, right, the local ablative therapies that has to be done at a center that’s close by and from what you’ve explained, that’s only for the short duration of time, whether I’ll have that local surgery or the ablation, or the radiation that I’ll go to that center, have it done, and then I can come back and continue all the rest of my treatments here. What about imaging? Where will I have to do the imaging?

Dr. Kathryn Hitchcock 39:11
Imaging can also be done close to home.

Manju George 39:15
Okay, great. This is this is really very, very patient friendly and patient centric design.

Dr. Kathryn Hitchcock 39:21
Exactly what we were going for. Thank you, you just made our day by saying it. And again, that’s because you all weighed in and made your opinions known. Without your input. We could never have made it that way. We’re so grateful for the time that people took to educate us on that.

Manju George 39:39
So what else can we do to spread the word about the trial, like, how can we help?

Dr. Paul Romesser 39:44
I think we just want patients to know about it. That it’s an option, that it’s maximally flexible, it’s pragmatic. We’re not here to put up barriers, we’re here to break them down. And we hope that you know, even if the trial is not open where your primary site is, you’ll talk to your doctor about it. And we can link you up with some, you know, locations where it’s open. And, we hope to see that, you know, it’s not only at big kind of cancer centers, but that it’s kind of spread out around the country, and patients kind of come in for, for this trial to seek out TAT, or at least to help assess the question.

Manju George 40:32
Okay. Okay. Thank you very much. As I was talking, so we have on COLONTOWN university, we have this diagnostic and surveillance test Learning Center. It’s a different topic. But where I was going with this is that, so we had like, for example, when we started when patients started using Signatura, not everyone was ordering the ctDNA test. But then what we did was that we asked patients to let us know where all they were getting the test. So then we actually put up a list of centers where they were getting the tests. So any new patient, when they wanted the tests, they could go and check to see whether there was a center close by. So I think that one of the things that we can do to facilitate, you know, people knowing about it is, as soon as you know that there is a site open or you know, certain techniques can be done in a particular place, if we can provide a list, you know, where all what is available, then that would be very helpful, because then people could go and click on it and find out, you know, how far it is for them. And I think that might facilitate, you know, more people knowing about it and enrolling. So that should be something that we could do on COLONTOWN University.

Dr. Kathryn Hitchcock 41:41
That sounds great.

Dr. Paul Romesser 41:43
And I’ll add one more thing some big centers have, like I know, in New York, and I’m not trying to plug my own Center, but I know in New York, we have the American Cancer Society has something called the Hope Lodge, which is a free lodging. So it’s not just unique to my center, it’s available to anyone with cancer, who comes to New York City for treatment. And so there are resources, if there’s not something close to home, where we could find other additional options for patients. And I think there’s many Hope Lodge equivalents around the country, and many great sites that we could try to put together to increase options for patients as well.

Manju George 42:25
I think that’s a great idea. Any other questions, comments? Yeah. So we’ve worked with, you know, Dr. Miller, and Dr. Romesser, and Dr. Hitchcock. So we have this trial design and more details about this trial up on feature trials on COLONTOWN University. So if you wanted to, you’ve heard whatever you heard them speak, and then you wanted to, you know, look at those, the details and, you know, when you have time, you can go over there, and it’s there. And Betsy will post, you know, I think one of you will send me the slides. Right, then I can send it to Betsy and Betsy will post the slides in Lungston. And yeah, in all the relevant metastatic groups, yeah, that would be great. So there are multiple ways that people can know about it. And then the other thing that we’ve been doing in COLONTOWN is that when we have newly diagnosed patient join, when we actually have an onboarding, so we asked them, you know, to tell us about where they are and what’s going on. So when we come to know that they might be eligible for certain trials, then we tell them, that there are these trials, because many times, you know, when patients join, they don’t know anything. And, you know, it’s sometimes they won’t come to know about it. And trials are not, you know, in general, people think that trials are something that, you know, when you have failed all lines of therapy, that’s when they should do it. So we try to tell people about firstline trials like this. So that’s another place that we would be talking about it. Yeah.

Dr. Kathryn Hitchcock 43:56
That is perfect. I’m so grateful that this whole system exists that you guys have put so much work into it. And the good that comes out of that just can’t even be measured.

Dr. Paul Romesser 44:08
Thank you, Dr. Miller, do you want to comment on the insurance and the insurance review that you all did with through Alliance as part of activating the trial?

Dr. Eric Miller 44:19
Yeah, so that’s a great question. So they do an insurance analysis to make sure that aspects of the trial will be covered. And we went through that analysis and everything checked out. Now, of course, you know, before any treatment, of course, they would do a prior authorization to make sure that all treatment would be covered. But there really isn’t anything on this trial that is really experimental, all the local therapies or established therapies that would be covered by insurance. Yeah, that’s a great question. Great question.

Manju George 44:55
One of the things I think we can also do is, as people start, you know, six months A year from now. And when we find like, we also have in COLONTOWN, Betsy is one of the Cabinet members. So we have a group of patients and caregivers who run the day-to-day activities in COLONTOWN. So we have something called the Alanna project, which is basically a place where we keep track of who all are in what all trials, and, you know, they will post updates. So if they have a clean scan, they’ll post if they have a progression, they will post so this way, you know, when a new person who wants to find out about trials, they can go and look in the Alanna project and find out if other people have been on the same trial and what their experiences are. So once we, you know, a couple of, you know, one year or something after the trial is open, we’re hoping that we will get to hear from patients, right, how this is going, if there are concerns? So I’m hoping that we can bring that back to you. And you know, if there is something that is in the way, maybe I don’t know, you can do an amendment or, you know, you can at least find out if there are ways to help, you know, for people to get over that block, whatever that is, right?

Dr. Kathryn Hitchcock 46:08
Yes, if there are barriers, we really want to know about them as soon as possible. Because you’re right trials, it’s not like you write a trial, and it goes through as written from the beginning. There’s always amendments, when we figure out that something didn’t work quite the way that we thought it was going to. So please, that would be wonderful. If folks would communicate with us in that way.

Manju George 46:30
We can, we can certainly think of collecting information, because I think, overall. So I would like the three of you to tell us, you know, how, you know, in your mind, like when we have the results? What are you hoping for the field from this trial? You know, like, how is this going to be practice changing? I mean, if you could comment.

Dr. Eric Miller 46:50
Yeah, I guess I can, I can start. I think for us, the big thing is just clarifying the role of local therapy in patients who we wouldn’t necessarily think about local therapy for. So if it’s shown to be beneficial, then we should be offering this therapy to more patients. So one of the impetuses for this trial was that, for the for the vast majority of metastatic colorectal cancer patients, you know, there aren’t really new drugs right now, you know, systemic therapy is sort of at an impasse. And so if we can come up with a different method, we can offer local therapy and improve survival, we need to figure out the patient population that’s going to benefit. And the kind of converse of that if we’re doing things that aren’t helpful, that are just adding toxicity and increasing the cost to patients. And we probably shouldn’t be doing those things. I’ll turn it over to Dr. Hitchcock & Dr. Paul Romesser.

Dr. Kathryn Hitchcock 47:43
Now, I’d say part of that we’ve kind of touched on today in that. I know a lot of patients in the process of dealing with this specific disease situation, don’t ever get a treatment break. And that was kind of where the idea came from originally, not just the chance for curative potential. But if that doesn’t happen, are we able to at least give patients a long, meaningful period of time where they’re not constantly in the hospital and dealing with doctors. So at the very least, we’re hoping we can achieve that.

Manju George 48:15
Dr. Romesser, do you have something to add?

Dr. Paul Romesser 48:19
I think they summed it up really well. I mean, it’s, I think whether it’s unique, and that whether it’s positive or negative, I think it’s going to impact how care is administered. Obviously, we spent a lot of time working on this, and we’re very passionate, we have every reason to believe this is going to be positive. But I think we can learn from both ways. And so we’re just really kind of humbled by the opportunity to run this trial and to offer this to patients.

Manju George 48:53
Thank you. I think that one question is, Is this only for first-line patients? Or is this also for patients who have had other treatments?

Dr. Paul Romesser 49:02
It’s predominantly first-line unless they had other treatment for stage one, two or three colorectal cancer?

Manju George 49:11
Okay, so I was thinking that like, I really liked what, you know, all three of you said, so, from a patient perspective, what you’re really saying is that right now, when somebody is stage four, you know, we hear this chemo for life, right? That’s what we hear for a lot of patients. So basically, what you’re trying to do is, you’re trying to break that big group of stage four patients into smaller subsets, to see if there is a group that you can treat many of their mets locally, so that they don’t have to be on chemo for life. They have these treatment breaks and hopefully, you know, the best-case scenario would be they’re cured by it. The worst case scenario is that they get a treatment break and the disease comes back after a long period of time. So then, you know, that is essentially a long chemo break for them, and that adds to their overall survival. Have I kind of summarized it?

Dr. Kathryn Hitchcock
That’s it. Exactly.

Manju George
Okay, thank you. Any any parting comments from the listeners?

Betsy Post 50:14
This is Betsy and I am the Community leader for the metastatic groups. And I’m really excited about this trial. And for all the reasons that you said, and I’m just, I don’t know, this is exciting. And I think patients are going to be very excited about the trial, and I’m happy to share the information. And you know, especially with the initial onboarding, we do get a good sense of some of these patients and the extent of disease and, you know, try to talk to them immediately. Because it’s such a good opportunity when they come to us new, and you’re able to talk to them about treatment options. And so I think, you know, this is great. I mean, it’s, I keep saying exciting, but I am excited, because I’ve been doing this a long time. And I think that there is a real need for this. It needs to happen, like you said, so I’m appreciative of all you’re doing.

Manju George 51:09
Thank you so much, Betsy

Dr. Kathryn Hitchcock 51:12
It’s good to hear you’re as excited as we are. We are on the edges of our seats, for sure.

Dr. Eric Miller 51:20
I think it’s a great point about it being first line and not necessarily thinking about trials when you’re first diagnosed. So I think if we can let patients know about it early to potentially give them an opportunity, I think that is that is exactly what we’re hoping as well. So thank you.

Manju George 51:37
Yeah. Okay. So I think then we can thank everyone, and thank you. Thank you. Thanks to everyone for joining and thank you, doctors, Hitchcock, Miller and Romesser. And I hope that, you know, with all of this, we will be able to tell patients about, you know, we hope to be able to take this information to the most number of patients and, you know, kind of help with enrollment too that, that’s, I hope that’s together, we can, you know, get the trial enrolled and, you know, get everything going quickly.

Dr. Eric Miller 52:18
Thank you. Yeah, thank you so much. We’ll send the slides. Okay.

Manju George 52:23
Okay. Thank you very much. Have a great day. Thank you. Bye bye.