COVID-19 Causes Shifts in Clinical Trial Practices

Shilpa Gupta, MD

The increasing severity of the COVID-19 pandemic has prompted shifts in the treatment of patients with cancer, according to Shilpa Gupta, MD, with some patients delaying therapy to avoid potential exposure to the virus and clinical trials being put on hold until further notice.

Clinical trials have also been greatly impacted by the COVID-19 crisis. Some research efforts have been able to convert to a virtual schedule with patients, but others have been put on indefinite pause. Patients enrolled on some of these trials who are receiving oral medications and achieving benefit, are being mailed their drugs so that they can avoid coming into the clinic. Additionally, if these patients need blood work and other testing done, they have been recommended to have it performed locally, rather than at the clinical trial site.

“Every day is a new day and we have really tried to adapt how we practice based on the challenges we are facing,” said Gupta. “As oncologists, we have to balance the risks and benefits of keeping patients on track with their treatment. However, at the same time, we need to remember that 1 hospital admission for a frail patient amidst this COVID-19 crisis can be fatal; we have to weigh [our choices] accordingly.”

OncLive: How has COIVD-19 been impacting your practice in Ohio?

How has the has the transition to virtual meetings been for you and your patients? Are you facing any specific challenges?

The situation with COVID-19 is rapidly evolving. What have been the most recent changes made in your practice?

There has been news regarding shortages across healthcare systems in terms of face masks, gowns, and other equipment. How are you handling that?

Have any of your patients tested positive for COVID-19 thus far?

How are you currently determining whether the symptoms are associated with immunotherapy or the virus?

You treat patients with genitourinary cancers, and you spoke about modifying some of your treatment plans to avoid putting your patients at risk of infection. What are examples of some of the treatment modifications that you have been making for your patients?

How is COVID-19 impacting the administration of immunotherapy specifically?

In an interview with OncLive, Gupta, staff member of the Department of Solid Tumor Oncology of the Cleveland Clinic Taussig Cancer Institute, discussed the modifications made to patient care in light of the COVID-19 pandemic, the hurdles faced with clinical trials during this time, and some of the ways in which her institution is facing the virus-related challenges head-on.Gupta: In my own practice, I try to prepare a few days ahead of the visit to see whether the appointment can be converted to a virtual visit. At our institution, we have the capability to conduct virtual, face-to-face meetings with our patients and we’re also doing more phone visits. If some new consults can be done virtually, I'm trying to do that, especially for patients who are coming just for a second opinion; then they can prevent making that trip. I want to minimize the points of contact for my patients. For those in whom treatment cannot be delayed, we are trying to do that virtually as well and have them go to chemotherapy infusion.Sometimes we experience some technical challenges and then we resort to the good old phone call discussion, but patients really like [virtual meetings]. They prefer to see the doctor's or provider’s face; it gives them some reassurance, so we try to do that. Some of them want to do FaceTime if the virtual app doesn't work, which we have also been doing at times.We are seeing more changes as the number of admissions increases, but our institution is doing a great job with keeping us updated on a day-to-day basis. We know where the hospital capacity is in terms of admissions. To serve that purpose, we are trying to ensure that our clinics are well-planned. For patients who have more risks than benefits with regard to receiving any treatment, we are trying to withhold or defer their treatment to avoid any treatment-related admissions, as that would not be in their best interest. Furthermore, we are minimizing the traffic [in the clinic]. All patients, visitors, and providers are screened at the entry point every day with a temperature check. We are trying to screen as much as possible. Also, when I'm in a room with a patient, I'm using masks to have that barrier protection.Fortunately, as far as using surgical masks, we don't have a shortage. The N95 [masks] and other protective gear we reserve for those who are taking care of patients in the intensive care units (ICUs). However, there is a shortage, which is unfortunate. We're trying to be judicious with the use [of these supplies that we have].So far, I've had a couple of patients who were admitted to a local hospital with pneumonia-like symptoms and we are still trying to figure out if [their symptoms are] related to COVID-19 or their disease. The challenge now is that for every differential diagnosis, COVID-19 [is a possibility]; the top priority now, especially for patients on immunotherapy, is to see whether [their symptoms are] related to the treatment or to COVID-19.Patients who are getting admitted are being tested for COVID-19. Empirically, patients are being treated with steroids if there's a slight suspicion that [their symptoms] may be associated with immunotherapy; [we don’t think this] can hurt, [even] if they are also COVID-19—positive.For some of the patients with metastatic kidney cancer or bladder cancer who are on immunotherapy, had stable disease or a response in the past and are continuing to do well, I am deferring their treatment. I am doing this because data show that even if immunotherapy is withheld for a couple of doses, as we would if they experienced an immune-related adverse event, it's not going to harm them. This [only happens], of course, after I have a discussion with the patient about the risks and benefits [of doing so]. I’m also withholding treatment for patients who are on salvage chemotherapy and who are frail and at risk for hospitalization if they were to receive second- or third-line chemotherapy for prostate cancer. [Instead], I am continuing supportive care for those patients, as long as they are in agreement of doing that.Patients are cautious. They want to withhold treatment if they are able. In fact, some of our patients called us themselves and said, “We don't even want to do any blood work or anything until this COVID-19 [crisis] settles down.” There's a lot of news out there, and it would be good to get more information. The data that came out recently in The Lancet said that patients who were on treatment did worse in China, although we don't know many details of what that treatment consisted of. We do know that a majority of those patients had lung cancer. I am really weighing the risks and benefits [when I’m making these decisions].

Do you find that patients are educating themselves on the virus?

Many clinical trials have been put on hold or they're not recruiting new patients. How have you seen the clinical trial aspect of oncology shift during this pandemic?

In prostate cancer, we are not having patients who are just on leuprolide acetate or oral hormonal agents come in. I have a long discussion with them in which I tell them that it's okay to delay the leuprolide acetate if need be. Sometimes those patients are tougher to convince to delay the treatment. On the other hand, many patients want to delay leuprolide acetate because of the adverse events associated with it. It just boils down to having a balanced discussion. Patients are coming around to understanding the risks and benefits [of what is happening], and the fact that we are checking on them more than we usually do in between visits is also providing them with necessary reassurance.Many patients are doing that. [This whole situation is] most challenging for the patients who we are trying to treat with a curative intent, where the treatment does include surgery in the near future. Decisions regarding whether the surgery should be delayed in those cases are tougher to make. However, [we’re finding that] patients understand the risks and benefits. In my experience so far, patients are not pushing to be treated. Most of them are understanding that this is a bigger risk in their setting if the treatment were to have more adverse events requiring hospitalization.In our institution, we haven't halted new patient enrollment [on our trials], but we are using a common-sense approach with regard to this. For example, if a trial offers standard-of-care treatment plus [another agent], we are not enrolling on that study and we are propagating for standard-of-care treatment [to be given] closer to home [so] they [can avoid] coming from a long distance. For patients who are already on the trial, we are minimizing their study-related visits as long as they can get labs and scans done locally; then, we’ll [follow that up with] a virtual visit.

In terms of statistics or trends associated with the virus, what are you seeing in your practice?

What advice can you offer to healthcare professionals who are trying to navigate the COVID-19 pandemic?

In that regard, we are letting the sponsors know of our plan, and we are shipping the drugs to the patients if they are on oral medications. [We] anticipate many deviations [in this area], and our research leadership has enforced [how we all feel]: patient safety [comes] first. We will take care of the deviations per protocol. I must say that many sponsors are very proactive, as well. In fact, some companies have said, “Do not enroll patients until the end of April,” because they want to monitor the situation on their end, too. If patients are getting into trouble because of COVID-19 and being on active treatment, it’s not just a risk for the patient but also for the study in general.We are seeing, at least in our state and institution, that the inpatient hospital admissions are on the rise. That [falls in line] with the trend [we are seeing] that [leads us to believe that we will see a] peak in April and May. As such, [an increase in inpatient hospital admissions] is not unexpected; however, the number of patients who require ICU stays is pretty high. We want to be well equipped with triaging so that we are not using beds for patients who don't really need to be admitted.The advice here is to prioritize patient safety first and to do no harm. If we are giving a treatment that was going to improve their survival for a few weeks or a couple of months, is it okay to hold a cycle of treatment? That is the discussion we need to have.

I'm not by any means saying that we should delay curative treatments. I just saw a patient with testicular cancer last week, and we started him on the treatment right away knowing the risks and benefits. We have to triage accordingly. This is not the time to do everything [by the book], in an ideal way. We need to learn how to adapt to the situation and do what is best for our patients. Ideally, we would like to do many things differently, but we really need to learn how to do what we can for patients at this point.

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At Cleveland Clinic, healthcare personnel are working to transition over to virtual visits whenever possible so that patients can avoid unnecessary exposure to the virus. After weighing the risks and benefits of continuing versus delaying treatment, doctors and patients are coming to a shared decision regarding the next steps for care. For some, the benefits of coming into the clinic to receive intended treatment do not outweigh the risk of potential infection with the virus, and thus, more patients are staying home.