This story is part of The Cancer Letter’s ongoing coverage of COVID-19’s impact on oncology. A full directory of our coverage is available here.
As he manages the logistics of running Rutgers Cancer Institute of New Jersey and cancer services throughout RWJBarnabas Health, Steven K. Libutti has to worry about providing cancer care in a massive health system in the midst of the COVID-19 pandemic.
“We’re watching what’s happening in New York, because we know that’s our future here in New Jersey,” Libutti said to The Cancer Letter. “We’re starting to see a significant increase in COVID-19 cases, hospitalizations and ventilator use, especially the last three or four days.”
That day, April 3, New Jersey reported nearly 30,000 COVID-19 cases and nearly 750 deaths. The numbers have since climbed to 37,500 cases and over 900 deaths. The state is a distant second to New York, which has reported 122,600 cases and nearly 4,200 deaths.
In addition to making certain that the health system has enough beds, ventilators and N95 masks in anticipation of the surge, Rutgers and RWJBarnabas Health are initiating a clinical trial of azithromycin and hydroxychloroquine vs. hydroxychloroquine alone vs. supportive care for six days followed by hydroxychloroquine. The study’s primary endpoint will be viral load at six days.
The Rutgers study will accrue 160 patients, with an early look after 80 patients are accrued. Ultimately, the answer may depoliticize the COVID-19 treatment aggressively touted by President Donald Trump at his White House briefings. The trial will test the findings of an earlier study by French researchers. The French study was open-label and not randomized. Altogether, 20 patients were treated.
“The French study, while small, looked promising. Both agents are readily available, FDA-approved, and, for the most part, well tolerated,” Libutti said. “If a larger study can support the results seen in the French study, these agents can be quickly deployed as a component of the approach to treating COVID-19. If the larger study does not show activity, we can move on from these agents and focus on others.”
Cancer centers are especially well suited for getting quick answers to scientific questions involving COVID-19.
“We are structured to do exactly what is needed right now: to quickly and efficiently deploy clinical trials in a very structured way, with an infrastructure that allows us to carefully monitor them, to collect data in a very organized, efficient and regulated way, to be able to support the infrastructure required to put together a trial, and then safely conduct it,” Libutti said.
Libutti spoke with Paul Goldberg, editor and publisher of The Cancer Letter. The conversation took place on April 3.
Paul Goldberg: So, how are you?
Steven Libutti: So, we’re hanging in there. This is like a nightmare that you just can’t wake up from, but there’s a lot of teamwork, not just across our own program at Rutgers and across our health system, but across the entire state of New Jersey.
And we’re doing everything we can to keep caring for cancer patients amid this pandemic, and all the complexities that it brings in the care that has to be rendered to the folks suffering from COVID-19. We’re slugging away.
We’re watching what’s happening in New York, because we know that’s our future here in New Jersey. We’re starting to see a significant increase in COVID-19 cases, hospitalizations and ventilator use, especially the last three or four days.
And we expect that we’ll see a peak in northern Jersey first, and then it will begin to flow down the rest of the state, central and south. We’re already seeing lots of cases in central Jersey, and we expect it to get worse before it gets better.
We’re looking at a very large state that’s your catchment area. What are the geographic patterns you are seeing?
SL: Not surprisingly, we’re seeing COVID-19 cases increase significantly in the northern portions of the state, the ones in closest commuting proximity to New York, to Manhattan, and it’s traveling south on I-95, the Jersey Turnpike.
And so, where a lot of our cases were in the northern portion of our catchment and our health system, we’re now seeing more cases in the central region, and a slight pickup in cases, much like in locations further south.
We expect that those southern locations are going to see the wave as well. Probably, we’ll see the peak, as best as we can assess by the trends, in the north over the next week. And then the central region, probably over the next week-and-a-half to two weeks, and then the southern part of the state in two-weeks-plus.
We’re really bracing ourselves for a surge of cases. As everybody has predicted, this is a huge strain on resources, not just beds and ventilators and ICU, but personnel—nurses, providers, all being asked to now care for critically ill patients with COVID-19, and, as I said, we’re doing everything we can to maintain cancer care, because that’s still critically important.
Cancer is not going to take a break or sit on the sidelines and wait for us to finish dealing with the pandemic.
What’s the number of cases you’re expecting?
SL: It’s hard to say, because the patterns are different from each hospital and each region. New Jersey caseloads right now, and all of us, I think, are essentially following the same data streams, [including] the Hopkins School of Public Health program, looking at case numbers across the world.
I track that every day, and New Jersey today [April 3] is close to 30,000 cases and almost 750 deaths.
And this is always lagging behind by about a day, as they catch up with all the data from the hospitals. New York state’s over 102,000 cases [April 3] now. So, between New York and New Jersey, we make up just under half of all the cases in the United States. But I don’t think it’s going to be isolated to us.
I think that the rest of the country is looking at a preview of what to expect as the cases and the virus spread across the rest of the United States.
I don’t know where we’ll peak. As you know, we’re one of the more densely populated states, but unlike New York, where Manhattan is very tightly and densely populated–a lot of apartment buildings etc., where it’s ripe for transmission—we have urban areas and rural areas.
How this all maps out in New Jersey and what our ultimate peak is in terms of numbers is tough to say, but it’s going to be more, we’re not at the peak yet, and we will see a lot more cases.
Is your hospital capacity holding up?
SL: So far, we are. I think it’s part of the strength of being a system, having 11 hospitals, geographically deployed across the state. Some of our hospitals are really bearing the brunt of large volumes of patients admitted, with a fair percentage at each of those hospitals in the ICU and on ventilators.
But, fortunately, some of the other hospitals in our system, especially some of the ones that are a little further south or west, aren’t seeing the same numbers yet. And so, we’re having to come up with a process to move patients around throughout the system, with respect to cancer care, trying to maintain cancer care at the hospitals that are busy with COVID, but also looking into how we move some of our cancer services to other hospitals within our system.
I’ll also mention that a week ago, last Friday, we initiated a weekly statewide cancer teleconference across all the programs, or at least as many of the programs as we can get to participate—and it’s almost 100% of the cancer programs across the state.
So, all the major health systems and their cancer programs, leadership and key players at their cancer programs get on a teleconference every Friday morning—today was our second one. We started last week.
We’re sharing what experiences we are having, where we have common problems that we’re facing, how we might all work together to try to come up with solutions to those problems, how we are looking at the surges we’re seeing and how we can maintain cancer care.
We are trying to work together as a state, to make sure that we can continue caring for cancer patients, acute and otherwise, for as long as we possibly can, and, hopefully, continue to maintain cancer care throughout the pandemic.
Are you having any shortages of equipment so far?
SL: I think everyone is struggling with things like PPE (personal protective equipment), especially N95 masks, surgical masks.
I can’t speak for the other systems across New Jersey, but I can say from our system’s perspective, we have supplies. We’re constantly keeping track of inventory, on a day-to-day basis, and leveling it up, both to the leadership at Rutgers and the leadership at the health system, to make sure that they’re acquiring supplies as we need them, whether it’s from the state or from vendors.
So, I think we’re, right now at least, keeping ahead of the need for supplies. Ventilators right now, I think, we’re keeping up, but, again, we’re not at the peak yet, and how that plays itself out over the next couple of weeks, we’ll see.
I know, the governor and his team are working hard to make sure that all the hospitals in the state have the equipment they need, but we’re going to have to see how this plays out. Certainly, if we get the kind of numbers they’re seeing in New York, it’s going to stretch all of our systems very thin.
What about the underserved versus the wealthy? Are you seeing anything on that, or are you even looking yet? It’s probably very early to look.
SL: We are, as a system, always need-blind and seek to serve our entire community. And we certainly don’t turn folks away, and never have, coming to our ERs and coming to seek care from us. In terms of disproportionate numbers of infected or severity of disease, I don’t think anyone has had time yet to take a deep breath and look at that.
I think we’re seeing infections across all socioeconomic layers and all ethnic groups, etc.
This is, so far, an equal opportunity pandemic, in terms of the folks that are getting affected. So, right now, I wouldn’t have any specifics in terms of demographics, but we’re seeing patients from all over our system and all walks of life—all socioeconomic strata, in terms of those affected.
How are your cancer patients doing?
SL: We, fortunately, have not yet seen a lot of our cancer patients under care get infected or succumb to COVID-19. That is one of our principal concerns: staying ahead of that. I’m alluding mainly to our patients under active care.
I’m sure that if we went back in the histories of the patients that have been treated so far across the system and some of those that have succumbed to the disease, there may be cancer history in their background, because of how common cancer is.
But right now, our patients under acute cancer care, while we’ve had some patients infected, we have been keeping ahead of that, in terms of not having a lot of patients suffer mortality, in terms of our acute cancer patients.
Hopefully, that’s not just a matter of time and numbers, that we can aggressively stay ahead, with the various practices we’ve put in place to try to mitigate spread of SARS-CoV-2 in cancer centers.
We are practicing social distancing. We are implementing telemedicine to try to minimize patients coming in for follow-up visits, routine visits. We are going to be launching this week using telemedicine for new patient visits. Again, we are trying to minimize the number of patients that have to be together.
And then, obviously, our patients getting radiation therapy or infusion therapy, we are trying our best to expand space, to increase distance between patients. We’ve implemented some policies minimizing or severely limiting folks that can accompany our patients, again to maintain social distancing, and then, making sure our providers and our staff are appropriately gowned and masked, eye protection, patients wearing masks, again, trying to minimize the risk of spread.
We’ve been talking to a physician in Milan, and their approach was to set up a COVID-free hospital, as best they can, for cancer patients. Is that doable? Is that the way other people should do it? Have you looked at them at all?
SL: You know, we talked a little bit about that on our statewide call, and I think it will be challenging to do that; maybe not impossible, but certainly challenging.
I think we’re certainly going to try to—just because it will make it easier to treat COVID patients and to have teams focused on their critical care needs—I think we’re going to try to coordinate certain hospitals across the state that will focus on COVID response.
And there’s also plans in New Jersey, like there are in other states, to set up “field hospitals”, or expanded locations for COVID patients. I think that will allow us to identify certain hospitals, where we can concentrate the non-COVID patients, and certainly cancer patients.
I don’t know that we’ll be able to totally segregate COVID patients, or create a single hospital that is only for cancer patients. As you probably know, we have plans in place now at Rutgers and RWJBarnabas Health to build a freestanding cancer hospital in New Jersey, but, obviously, that’s three years away.
By then, hopefully, this is just a bad memory, in terms of what we’ve gone through here. But right now, there are no active plans to designate one or two hospitals purely for cancer care. But that may be something we have to think about. I’m aware of the data from Italy and from Spain, in terms of the mortality rate in lymphoma patients and in lung cancer patients, and that’s why we’re trying our best to keep our teams separate.
Right now, at least in New Brunswick, oncologists are not on the COVID acute care teams, even though there’s a surge plan that’s been put in place for docs that don’t normally do critical care and infectious disease work to be able to surge to help with COVID care.
Our oncology doctors may ultimately have to participate in that, but right now, our whole mindset is to try to keep them separate and caring for the cancer patients. At least for now, so we’re not putting the cancer patients at risk.
Any other best practices you’d want to propose or any that you’ve benefited from?
SL: Well, most of them are the common-sense ones. We call all our patients that have appointments with us, whether it’s radiation oncology or an infusion therapy, we call them the night before their visit—every patient—and we go through a questionnaire about any symptoms they may have, have them take their own temperature to note any fever.
We screen every patient at the door, before they come into the cancer center, with a history and another temperature check. We do the same with our providers that have clinical activity.
Every morning, everyone gets screened. Everybody—both provider and patient—are all masked, to try to decrease the risk of spread for anyone who’s asymptomatic and might be a carrier.
We actually have a pretty interesting study ongoing through our CTSA [Clinical and Translational Science Award], led by Reynold A. Panettieri [vice chancellor for translational medicine, science director, Rutgers Institute for Translational Medicine, science professor of medicine, Rutgers Robert Wood Johnson Medical School, emeritus professor of medicine, University of Pennsylvania], Jeffrey Carson [provost, New Brunswick at Rutgers Biomedical and Health Sciences, the Distinguished Professor of Medicine and Richard C. Reynolds, M.D. Chair in General Internal Medicine] and Martin J. Blaser [director of Center for Advanced Biotechnology and Medicine, the Henry Rutgers Chair of the Human Microbiome, and professor at the Departments of Medicine and Microbiology, Rutgers Robert Wood Johnson Medical School] that is studying health care providers, or health care workers.
The study is looking at asymptomatic health care workers without necessarily a known exposure and testing all of them for SARS-CoV-2, and the idea is to enroll 700 providers or health care workers. So far, I think in the first week that trial has been open, they’ve enrolled 500 already, and the goal is to try to determine what the prevalence of SARS-CoV-2 infection is in an asymptomatic cohort of health care workers. Just so we can get a sense of how pervasive asymptomatic infection is.
I think that’ll be a really important study in terms of understanding, risk mitigation and how well we are doing and what we might do better. That study dovetails into two other studies, one of which we launched this week. The other is going to launch in a week or so.
This week, we launched a therapeutic trial that’s not just for cancer patients. It’s for all patients that have SARS-CoV-2 and COVID-19. It’s being run by Rutgers Cancer Institute. I am the study chair. [The study will randomize patients into three groups: 1) azithromycin and hydroxychloroquine; 2) hydroxychloroquine alone; or 3) supportive care for six days followed by hydroxychloroquine. Treatment will continue for 10 days. Once treatment is completed, participants will be followed monthly for six months to monitor for return of symptoms.]
I wrote the trial with collaborators, and a critical care doctor, Sabiha Hussain, is the PI, and we’re essentially looking at hydroxychloroquine sulfate plus azithromycin versus hydroxychloroquine sulfate versus a supportive care arm, with the endpoint of the study being viral load at day six, compared to baseline, essentially trying to mirror the study that was done in France that seemed to indicate that there was some antiviral activity with the combination of azithromycin and hydroxychloroquine.
The trial will enroll 160 patients, and I think it’s real important that in a prospective randomized way we understand if those agents are actually effective at reducing viral load, and if so, then make some solid recommendations on how to use them and when to use them. It’s my own suspicion that the antiviral agents will best be applied early in the course of the disease, not when patients have had progressive pulmonary disease, ARDS, requiring ventilation.
At that point, we’re probably dealing more with the consequences of the immune response and cytokine release and less so with viral load. But, certainly, early on in the disease, I think antivirals can play an important role. Agents like hydroxychloroquine,
maybe with azithromycin, agents like remdesivir, and, obviously, there are many trials ongoing [The Cancer Letter, March 24, 2020].
I should mention that in the therapeutic trial that I just talked about, we’re accruing now and went from concept to an IRB-approved protocol in nine days. The IRB and the FDA were just superb in working with us to try to get this done in a safe way, in a rapid way, so we could start answering that important question very quickly.
How and why did you choose these two drugs, as opposed to some other drugs? Is the French study intriguing enough? I am not trying to drag you into politics. We can just stay on science.
SL: The French study, while small, looked promising. Both agents are readily available, FDA-approved, and, for the most part, well tolerated. If a larger study can support the results seen in the French study, these agents can be quickly deployed as a component of the approach to treating COVID-19. If the larger study does not show activity, we can move on from these agents and focus on others.
How quickly do you think you can get the answer?
SL: So, we have to accrue 160 patients—it’s my goal to accrue all 160 in about 30 days. As I said, we started the trial this week, and our goal is to have patients completely enrolled, if we can, by the end of April. And then, since our endpoint is viral load on day six, compared to baseline, we hope to have all the data generated within the couple of weeks after the trial is completed.
If I can get an answer to this question by mid-May, I think it would be very helpful. And so, that’s what we’re shooting for. Obviously, you can’t control a lot of things, like accrual and samples, etc. We have a really good team in place, a very good infrastructure. And so, that’s my goal, hopefully, to have an answer within the next six or eight weeks.
You can probably shorten that by a few weeks, because it’s not a rare disease you are treating.
SL: That’s right. In fact, we have a stopping rule. After we’ve accrued 50%, we’re going to look at the results—after 80 patients have been enrolled—and so, there’s the possibility that we’ll see such an extreme response that we might be able to make some decisions based on efficacy. Or if we see no difference between the arms—between the arms and our supportive care arm, we may be able to declare futility.
I think either answer is going to be important to know. If these agents are effective, we need to know that, because we need to use them, maybe earlier and more broadly. If they’re not effective, we should also know that, because we shouldn’t be spending time administering these drugs if they don’t work.
The Cancer Letter would be the place to cover it—because we would get the answer right away to everybody.
SL: When we know what’s coming out, I’ll reach out to you and let you know. We’ll obviously prepare it as a manuscript, but it’s so important we’re not going to wait until it gets published to get the information out there, because it’s going to impact and affect decision making. Well, I’d be happy to let you know as soon as we know.
We’ll get it out within hours of you letting us know to everybody in the field.
SL: That would be great.
I’m wondering why you didn’t choose to work with more sites or more institutions in accruing patients.
SL: We may very well do that. We’ve opened it at two sites within our system. We opened it at University Hospital in Newark and at Robert Wood Johnson University Hospital in New Brunswick.
We may yet open it at other sites across our system, and I’ve had conversations on our statewide call about opening it at other hospitals across the state. It is not an easy trial to do logistically, because these are highly infectious patients, and they’re patients with symptoms, when we get these samples—and we get samples at baseline, day three and day six—our team has to be entirely in PPE. They have to take oral pharyngeal swabs, they take blood.
So, logistically there’re some hurdles that you have to put in place to be able to do it. But I think if we have any trouble at all accruing at the pace we’d like to accrue, I will quickly reach out to open it at other sites.
You’re an immunologist; what’s your next trial? Because the next rabbit out of the hat is going to be immunology; no?
SL: I can’t really honestly with a straight face carry the moniker of immunologist. While I have a strong interest in cancer immunology, and I am a basic scientist in addition to being a clinician, there are far more qualified immunologists that are actually trained, and have a much stronger background than I.
But I will say that I think this is obviously a problem of immunology and a problem of microenvironment and response to a pathogen. And so, it’s been very interesting to me, in terms of the new collaborations I’ve been able to start at Rutgers, as we’ve all tried to rally together to face this pandemic.
I think that there are opportunities to understand better ways of vaccinating patients, and we have a collaborative project that we just launched this week—looking at novel approaches to vaccinate patients. We’re looking at how serology either indicates which patients will be at risk once they’ve had this disease to be re-infected, or which folks might already carry some immunity against this pathogen.
As you know, there’ve been some publications around, perhaps BCG immunization might confer some protection against this, and so collaborating with an investigator Maria Gennaro, [professor of medicine] who has a particular interest in this at Rutgers, these are going to be some of the questions we’re going to look at moving forward. The idea of treating patients who are virus-positive but asymptomatic, prophylaxing patients against progressing into COVID-19 is something we’re looking at.
Jeff Carson, one of my colleagues, is writing a protocol looking at hydroxychloroquine and azithromycin in the asymptomatic population as a means of potentially preventing COVID-19 disease.
Paul, I would have never predicted six months ago, as a cancer center director and a surgical oncologist, that I would ever write a trial looking at agents against an infectious disease. But we’re in very strange times right now. But I have to say, everybody is standing up together to try to face this issue.
I emailed Ned Sharpless, the NCI director, on a Saturday two weeks ago to tell him about the trial we were writing, and asked for some guidance and support from NCI. And within literally 12 hours, he and Henry Ciolino [director of the NCI Office of Cancer Centers] put out [a request for P30 supplement applications under the NIH standard Funding Opportunity Announcement (PA-18-591)], essentially asking the cancer centers to submit ideas for going after SARS-CoV-2 or COVID-19 either directly related to cancer issues with it, or even not just cancer, but finding new therapies. And so, that was amazing.
The FDA and the NCI are working together to try to test new antibody assays, and we’re going to be through an [Material Transfer Agreement] providing them with positive sera and negative sera to use as controls in that. So, the number of groups that are standing up and standing together to face this worldwide pandemic is amazing.
And it really is a testament to the power we have when we all try to work together to face an unprecedented challenge, and this certainly is an unprecedented challenge.
Let’s talk about the cancer centers for just a moment, about the role they can play in this, because there’s really nothing like this infrastructure anywhere else in medicine—the infrastructure for asking questions, setting up experiments, and getting the answers fast.
SL: You are absolutely right. That is spot-on, and I think the reason why I got involved with this four weeks ago, was essentially that recognition at Rutgers, and this is true at every cancer center, every NCI-designated cancer center across the country.
We are structured to do exactly what is needed right now: to quickly and efficiently deploy clinical trials in a very structured way, with an infrastructure that allows us to carefully monitor them, to collect data in a very organized, efficient and regulated way, to be able to support the infrastructure required to put together a trial, and then safely conduct it.
Whether it’s clinical research assistants, or research nurses, or data managers, or our regulatory affairs folks, each of the NCI-designated cancer centers has been built to do the kind of fast, efficient and effective clinical research that’s necessary to answer questions.
And right now, there are some critically important questions that are not necessarily related to cancer, but we serve as a resource to our communities, to our states and to the federal government, since we are NCI-sponsored and designated to pull together in an emergency like this and leverage our expertise to help in any way we can.
And it’s not only on the clinical research side, but on the basic science side. As cancer immunology has become a major area of exploration at many cancer centers, you’re right, we have some very strong immunology activity going on in our research labs, and to focus some of those assets that we have to particularly look at this question and this problem, and how we might tackle it, is something else that we can bring to the table.
So, we, and I think cancer centers across the country, are rallying to the cause. I think that many of them are stepping up and leveraging their infrastructure and their resources to help.
I guess one thing that I’ve noticed as an instant historian—because that’s what journalists are—is that virology, immunology, rheumatology and oncology are stomping around on the same street corner. COVID-19 showed that more than anything ever could. Am I seeing something that’s real?
SL: I think you are.
I think we in the cancer community have been gravitating closer and closer to folks that have for a long time been mavens of virology and immunology. We’ve been looking at it, not just virology as potentially causative agents of cancer, HPV is a great example, but also as vectors. How do we leverage vectors to immunize against cancer?
And it’s not such a leap to apply some of the same principles to immunizing against pathogens. Although there are amazing experts that have dedicated their entire careers to immunizing against infectious disease, I think there’s also things that have been learned in the cancer community that might help with that.
And I think HPV is a perfect example.
Here we have a virus that we know is a pathogen that leads to neoplasia and malignancy, and a lot of expertise has grown out of that, including the virology unit, an immunology unit at NCI Frederick. And now, that group is focusing on helping with the COVID-19, SARS-CoV-2 pandemic.
I think you’re right that we have gravitated to certain overlaps with immunologists, infectious disease docs. The microbiome is a great example. We’ve started to really embrace studies in the microbiomes in understanding cancer risk and response to cancer therapy.
And, obviously, the microbiome plays a huge role in susceptibility to infection and response to infection. And so, Marty Blaser, who’s a world-renowned expert in the microbiome, who’s now at Rutgers, and I had begun some collaborations around the microbiome and cancer, and now we are talking to each other almost every day about how we’re deploying efforts for SARS-CoV-2 and COVID-19.
So, I think you’re right. I think these groups that began to interact, as you said, on the same corner, are now really seeing what each has to offer in the current emergency.
I would have never predicted six months ago, as a cancer center director and a surgical oncologist, that I would ever write a trial looking at agents against an infectious disease.
Is there anything we forgot, anything we need to focus on?
SL: No, only that I think now, more than ever, is a time for collaboration and working together. I think the only way we are going to defeat this current pandemic and be ready for future ones is to really look at ways that we can work across disciplines, work across specialties, work across state lines, and across institutions, and really see the strengths we have when we work together and collaborate.
This is truly a nightmare, and truly something that is beyond words to describe. I could never have imagined in my lifetime seeing something like this, but I am optimistic that working together, we are going to get through this, and if we do it right, we’ll be that much stronger when we do.
Good luck and stay safe.
SL: Thank you, Paul. I appreciate it, and, as always, thank you for telling our story.
