Immunotherapy Clinical Trials with Dr. Ezra Cohen

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Clinical trials are essential to bringing promising new treatments to cancer patients, often for the first time or in new combinations with other treatments. However, there are many common misconceptions about cancer clinical trials, ranging from when patients can or should enroll, to placebos and even safety.

Ezra Cohen, M.D., chief of the division of hematology‐oncology at UC San Diego Moores Cancer Center, and co‐director of the San Diego Center for Precision Immunotherapy, addressed myths, questions, and other concerns during the Immunotherapy Clinical Trials presentation and Q&A session at the 2020 CRI Virtual Immunotherapy Patient Summit.  

During his presentation, Dr. Cohen explained that immunotherapy, or any type of cancer treatment for that matter, would not be available today without the participation of patients in clinical trials. All immunotherapy drugs go through three different clinical trial phases before being considered for approval.

Dr. Cohen encouraged patients to search for clinical trials from “day one” of diagnosis, explaining, “As soon as you have a diagnosis, one of the first questions you should ask your doctor is, ‘is there a clinical trial available to me? And can you tell me about it?’”

Cancer patients and caregivers may have picked up some misinformation around clinical trial enrollment, and Dr. Cohen went through some of the most common myths to allay their concerns. For example, some may believe that you will receive a placebo or sugar pill instead of treatment. Dr. Cohen clarified that placebos are rarely used instead of treatment and are never given in the absence of a treatment. He noted, “The only time that a patient on a clinical trial will get a placebo alone occurs when observation or no treatment is the appropriate standard of care.” However, he explained, this is very uncommon and a question that a patient should discuss with their doctor.

Following the presentation, Dr. Cohen answered questions from patients and caregivers in the audience. One attendee asked about the role of clinical trials for patients with rare cancers. Dr. Cohen explained that when we add up all rare cancers, they actually account for roughly a quarter of cancer diagnoses. This is a substantial number. In response, many large cancer centers in the U.S., including UC San Diego Moores Cancer Center, have opened up rare cancer clinics. Immunotherapy clinical trials for rare cancers are opening at a much faster rate and clinical researchers are, Dr. Cohen shared, showing some very promising results. For example, patients with certain types of pancreatic cancer have had encouraging responses in clinical trials. (Register for the December 5 CRI Virtual Immunotherapy Patient Summit to learn more about promising immunotherapy clinical trials for pancreatic cancer).

Tamron Hall wrapped up the session by encouraging patients and caregivers to use CRI’s Immunotherapy Clinical Trial Finder to find clinical trials for which they may be eligible and schedule a confidential consultation with a CRI Clinical Trial Navigator.

IMMUNOTHERAPY CLINICAL TRIALS SESSION TRANSCRIPT

Tamron Hall: Dr. Ezra Cohen from the University of California San Diego is here to tell us what clinical trials are and answer top questions submitted by you about the myths and facts of clinical trials. As chief of the Division of Hematology Oncology, and co-director of the San Diego Center for Precision Immunotherapy at UCSD. Dr. Cohen has extensive experience running trials and has seen firsthand how immunotherapy is transforming cancer treatment. Dr. Cohen, thanks for joining us from your home as well. We’re ready to learn about clinical trials.

Dr. Ezra Cohen: Thanks so much, Tamron. We’re getting used to a new world. That was a wonderful session by John, always learn so much from him. And it is my pleasure now to spend the next little while talking about clinical trials and then taking your questions. Really, one of the things that we want to answer about clinical trials during this session, and get a sense of what they are, what the purpose are, and talk about the facts and myths of clinical trials.

So first, you may hear about different phases of clinical trials and the phases go from 1 to 4, phase 1 being the earliest. And really what we’re looking for in the phase 1 trial is quite simply, is the treatment safe? These are usually smaller studies that enroll anywhere from 20 to 100 patients. And the big question here is, not whether the drug works, but whether it can be administered and what’s the right dose?

Now, of course, we look for a signal to see if a drug works, even in phase 1, and we’re delighted when we see that. But that comes really into play in phase 2. In phase 2, we’re asking, does this work? Does this treatment work? Does this drug work? Whatever the intervention is.

And then finally in phase 3, we’re asking, does it work better? Should this be the new standard of care or part of our standard of care? And usually phase 3 trials are a comparison to the existing standard of care or to some sort of a second treatment or other option. And there, we’re now talking about much larger trials in the context of several hundred, to even a few thousand. Now, one of the questions that often comes up is, is there a placebo involved? And we do see that sometimes, or actually quite often in phase 3 trials, sometimes in phase 2 trials, but almost never in phase 1.

To put it into context, here we see a cartoon of all the different cancer types where there has been an FDA approval for immunotherapy. And the point of this slide is not to read every individual cancer type or to enumerate the different types of immunotherapies that have been approved, but to give you a sense that the scope of where immunotherapy is being applied and how broadly that is. It truly is from head to toe now, literally, in all these different cancer types. And the second point to make here is that this would never have been possible without clinical trials. All of these cancers within the context of immunotherapy were tested in phase 1, 2, and then eventually phase 3 studies, to get approval for immunotherapy.

So now let’s talk about some myths versus facts around clinical trials. I talked a little bit about placebo, and one of the myths that often surrounds clinical trials is,

“I might only get placebo or a sugar pill instead of treatment.” 

And although that is true, the fact is, placebos on their own are rarely used and never given in the absence of some form of treatment. And the only time that a patient on a clinical trial will get a placebo alone occurs when observation or no treatment is the appropriate standard of care. One might see that in a setting where a patient has received, let’s say curative intent treatment, and the standard of care is to simply observe that person for recurrence or for absence of disease. If that’s the case, a placebo control arm becomes appropriate. But I would say that those studies are the exception and certainly not the rule.

Now, it may be possible that a patient receives a placebo in addition to standard of care therapy, but the point being, that even on the control arm, the person is receiving some sort of treatment. So in the reality of clinical trials, it’s actually quite uncommon for somebody to receive only a placebo. But of course, it’s a question that you should ask your physician.

The next myth versus fact is that “trials are only for people who have run out of treatment options,” a last resort, if you will.

And although trials do serve that purpose, certainly when patients have exhausted standard treatment, by no means are clinical trials designed only for people with no other options. Truly there are clinical trials in cancer for all types and all stages. In fact, there are even clinical trials for patients who are at risk for cancer and have not developed it yet. So, anywhere from the very early diagnostic stages of the cancer management, to patients who truly have tried standard of care and standard of care hasn’t worked. And it’s very important as a patient, and as a caregiver, to ask even very early on at diagnosis, is there a clinical trial that applies to me in this setting? Because we should not view clinical trials as a last resort. We should view it as a very important part of the therapy of cancer right from the beginning.

Another myth versus fact is that “I need to travel to a large hospital or cancer center to participate in a clinical trial.”

And right now that simply is not true. We have several different networks of clinical trial organizations across the country. And in fact, some of them across the world, to ensure that patients have the greatest access possible to clinical trials. Many of these studies take place at local hospitals, at community hospitals, at cancer centers that are literally down the street or around the corner or at doctor’s offices in all parts of the country, in both urban and rural areas. And in fact, to the credit of many organizations, the federal government, the national institutes of health, there has been a concerted effort to open up clinical trials to community organizations, to underserved minorities, and to rural areas, that traditionally haven’t been necessarily served as well by clinical trials. So that is really no longer true. Clinical trials are often available at your local doctor’s office, and it’s worth asking.

“My health insurance doesn’t cover the cost of care in a clinical trial.”

Well, that should not be the case. Because doctor visits, hospital stays, and certain testing procedures, may be covered by insurance. The research costs are typically covered by the clinical trial, or really by the trial sponsor. And in fact, there are laws, national laws, that were passed over a decade ago that necessitate payment for standard of care for a patient who is going on a clinical trial. That should never be a hindrance to somebody getting on a study. Now, it’s important to note, and it’s important to ask your physician, when you’re considering a clinical trial. What costs are covered by the study? What costs are covered by insurance? Because there may be different factors that come to play in terms of out-of-pocket costs to the patients. But the reality is that health insurance does cover the cost of standard therapy, while research costs are typically covered by the sponsor.

“Signing a consent form locks me into staying in a clinical trial.”

That is simply not true. The patient always has the last word and always has every right to do what they want, as long as it’s in the context of the study, when they enroll on a clinical trial. And what I mean by that, especially, is that a patient is free to change their mind for any reason at all, about participating in his trial at any time, before or during the study. That is the patient’s prerogative. It doesn’t matter if they do or don’t have a reason. They don’t even have to tell. They don’t even have to say the reason. The fact is that, the patient always has that right to withdraw from a study, just as they have the right to participate initially in that trial.

Now, I would say that if you are considering a study and you’ve consented to the trial, and certainly if you’re on the trial, please give careful consideration to participating and withdrawing, really to preserve the integrity of the study, and for your own sake, to see that you get maximum benefit from that participation. As I’m sure everybody is mindful and is thoughtful about participating, but it is important to keep in mind that your withdrawal from a study does influence the outcome of the research. And of course it could influence your benefit as well.

“I will be made to feel like a guinea pig experiment.”

Well, that should really never happen. It should be, and it’s paramount, to continue treating people on a clinical trial as patients and continue to have, of course, their best interests in mind at all times. The reality is that the overwhelming majority of trial participants say they were treated with dignity and respect, and report having a positive experience in a trial. This is by far the majority experience on studies. And in fact, there are now data to suggest that patients actually do better on clinical trials. Not only are they more satisfied, but patients participating in clinical trials actually have longer survival than their counterparts that do not. So there are advantages, potentially, to participating on clinical trials. And really, you should never be made to feel like you’re a guinea pig on an experiment.

“Clinical trials aren’t safe.”

Well, although there are toxicities and side effects of anything, including interventions as part of a clinical trial, but the rigor associated with activating a study and ensuring safety of patients is really tremendous. There are multiple safeguards in place, including the Institutional Review Board. This is a group of physicians and lay people who review every single study, even if there’s an amendment to the study. So even every change to the study, before it’s allowed to open at any center. There are things called Data and Safety Monitoring Boards, and now almost every study has this. This is an independent, external group of people, usually experts in the field. A statistician and a patient advocate or a lay person that looks at the data periodically as a clinical trial goes forward, and makes a recommendation on whether a trial should continue or should stop.

There’s an ongoing consent process to make sure that patient’ rights, safety and awareness are protected before going onto a clinical trial. And underscoring all of this is, of course, the FDA and their process for making sure that every clinical trial is approved at that level. So, the point being, that there are several different bodies, several different lines of individuals and committees, that assure that clinical trials, first and foremost, are safe to the people participating.

Let’s talk about informed consent for a moment, because it’s a very important part of the process. The key here, be bold and asking for details. It’s your treatment plan. I can’t emphasize that enough. Patients should feel free to ask questions. And in fact, there are different websites, including CRI, that have lists of questions that patients might consider asking before participating in a clinical trial. It’s critical to be your own advocate during this process and never, ever, should you feel shy about asking a question on a clinical trial. There’s no such thing as a stupid question, and there’s no such thing as an inappropriate question. This is your opportunity and your treatment plan. So please feel free to ask questions as much as possible.

And here is just a word on the process of clinical trials. Have all the facts. Here are some of the components of an informed consent document. I won’t read it at length, but all of these different elements are there. This is standard in order to get an informed consent document approved, all of these elements actually have to be there. So you should read the informed consent. You should ask questions, and no question is inappropriate.

“How can I find a clinical trial?” That’s very important. First, ask your doctor. Don’t be shy about asking, even if the answer might be no, or you expect that you’re at a center that doesn’t participate in clinical trials. I can assure you that there will be centers not far away. And you should ask your physician, “Are there clinical trials available for my current state?”

Contact the patient advocacy organizations, such as CRI. And here you see the phone number that you can call for a clinical trial navigator, or you can go on websites. Of course, there are many websites that can direct you, including cancer research.org, as you see there, or clinicaltrials.gov. Just a word about clinicaltrials.gov, that can be difficult to navigate. Sometimes it brings up a lot of results. Sometimes it brings up results that might not necessarily be relevant. But I would encourage you to look at that site as well, clinicaltrials.gov, and bring those results to your physician or talk to your family members, your caregivers, about the results that you get from any website.

Well, I think then we can now take some questions, and there are questions coming in. So please feel free to send questions in. And we’re getting one right here that says,

“Does a physician always have to make a referral for you to join a clinical trial?”

It’s not necessarily a referral in the sense that we think about it. A clinical trial has to be available. It has to be enrolling. And obviously eligibility criteria need to be met for you to participate. So in a sense, it’s a physician or a center having access to a clinical trial that would serve your purposes. Now sometimes, your physician might want to reach out to a different center or a different physician and ask, “Hey, I’ve got Mr. Smith here. Mr. Smith has this type of cancer or this type of situation. Does your center have a clinical trial that’s available?”

By the way, I should mention that this program is being recorded and sessions will be available on CRI’s YouTube channel the week after the event. And so, you’ll have an opportunity to review this material if you want to.

Here’s another question that’s just come in.

“What is the length of time you are generally on a clinical trial? Can you decide to stay on a trial longer if the treatment is working?”

Well, the length of time that a patient is on a clinical trial is really predicated by three primary things. First and foremost, it’s the patient’s decision. And as we talked about before, a patient is always allowed to remove themselves from a clinical trial if they want to. Second would be, how well the clinical trial is working for that patient. That is to say, if a drug is not working and the cancer unfortunately is growing, then it doesn’t make sense to continue the clinical trial.

And then third is side effects. Sometimes we run into a situation, although thankfully that’s not often, but sometimes we run into a situation where a patient has certain side effects from an intervention on a clinical trial, those side effects cannot be adequately controlled, and a patient has to be removed. So really those are the three main parameters that will drive how long a patient is on a clinical trial. That is to say, if they want to stay on, if the drug is working, or if they have a side effect that can’t be controlled.

In rare instances, a clinical trial will be a certain length of time. That usually occurs in some very specific settings. Often in settings where there’s no active cancer, and the treatment is extended for a specific period of time. But those are, again, the exception rather than the rule.

“Can you decide to stay on a trial longer if the treatment is right working?”

Well fortunately, most clinical trials will allow you to stay on as long as the agent is working. But if it doesn’t, there’s almost always an option to allow you to extend the therapy. It’s incredibly rare to be in a situation where you’re not allowed to receive an intervention that is benefiting you, even if the clinical trial is over. The few situations where that does happen is the drug can have some sort of safety signal that would make it dangerous for you to continue. But that’s really a pretty rare instance.

Here’s another question that’s just come in, and please I’d encourage you to keep sending.

“Can immunotherapy with other types of cancer treatment like chemotherapy and radiation?”

 The answer is definitely yes. We’ve seen this in multiple different cancer types in head/neck cancer, in lung cancer, in gastric, et cetera, et cetera.

Immunotherapy in fact appears to work quite well with chemotherapy. In terms of radiation, we’re still trying to figure that out a little bit. It has worked in some situations, it hasn’t worked in others. I think we need to learn a little bit about how to properly use immunotherapy with radiotherapy, but certainly when it comes to chemotherapy, we see some very nice interaction and positive data there.

Here’s a question about tumor genome testing. And as molecular profiling of tumors, or next generation sequencing, tumor genome testing becomes more and more widely available. And incidentally, I would encourage you to ask your physician, your oncologist, about that. But as it becomes more available, the question is,

“Will tumor genome testing hurt my chance of getting into an immunotherapy clinical trial?”

Well, I would say no. In fact, if anything, genome testing or next generation sequencing may actually open up the different clinical trials and increase your options for participating in a clinical trial. It really would. I can’t think of a situation where it would hurt your chances of getting on a clinical trial. Having said that, there are certain clinical trials, and this is becoming more and more common, that allow patients based on a specific genomic or some sort of biomarker eligibility. And of course, that would be tested as part of the clinical trial. But just be aware that those types of studies are becoming more common.

Here’s another question.

“At what point in my treatment should I start looking for a clinical trial?”

I mentioned this earlier, I would say right from day one. As soon as you have a diagnosis, one of the first questions you should ask, is there a clinical trial available to me? And can you tell me about it?

Well, we live in the time of COVID 19 and a global pandemic, and here’s a question about that.

“How is COVID-19 impacting clinical research? Is it still safe to enroll in a clinical trial?”

Well, in this country and in many countries around the world, clinical trials did shut down or slow down in the spring and early summer. I’m happy to say that certainly at our center, UC San Diego and almost every center around the country, now clinical trials are up and running robustly once again and clinical research is back on track. There are, of course, different precautions being put in place to ensure patient safety. In fact, and this is to the FDA’s credit, we’ve created a system where many of the interactions can be done virtually. For instance, informed consent. And more of the visits on clinical trials now can be done through tele-health rather than having the patient come in person.

In addition to that, I can tell you our experience or our precautions are, we are actually testing patients for COVID-19 before participation on an interventional clinical trial. We screen patients before they enter our center. We have a restricted visitor policy to minimize the number of people in the building. And fortunately, these precautions have actually been quite effective. And to the point where we have not seen, believe it or not, a case of COVID-19 in a clinical trial participant, at least at our center. And I think other places that are taking the appropriate precautions have the same experience, very, very low infection rates with COVID-19 in patients participating in clinical trials.

Here’s another question about rare cancers, very important.

“What is the role of immunotherapy for patients with rare cancers?”

Interestingly, when we add up all of rare cancers, it’s about a quarter of the patients who have a cancer diagnosis. So, although each individual entity might be rare on its own, when we add them all up, we’re looking at a substantial number. To address that, we have not only opened up a rare cancer clinic at our center, and there are other centers around the country that have done this. But we are opening up clinical trials, including national clinical trials, for patients with rare cancers to try and see how well immunotherapy works for those diseases. And from those experiences, we’ve seen some very startling results. For instance, for patients with certain types of pancreatic cancer, pancreatic neuroendocrine cancers, we’re seeing that immunotherapy is quite effective and probably would not have noted that type of experience without those clinical trials. The same is true of other cancers that are considered quote, “rare tumors”. So the answer is yes, immunotherapy can work for rare cancers.

Here’s a question about patients that have no evidence of disease. And we talked about this a little bit during the slides. There are many clinical trials for patients who don’t have evidence of cancer. The question is,

“Can I still enroll in a clinical trial for immunotherapy?”

And the answer is, definitely. As immunotherapy has shown benefit, as showed you in this slide, in multiple cancers in patients who have advanced disease, recurrence or metastasis, we’re beginning to move immunotherapy into earlier stages of disease. And this includes patients who, when we do a scan or when we do testing, we actually can’t find evidence of the cancer, but they may be at risk for the cancer coming back. And in those cases, immunotherapy can have a dramatic role. And we’ve seen that in studies in non-small cell lung cancer. We’ve seen that in patients with melanoma, and we’re getting hints of that in other cancer types that, in fact, immunotherapy can reduce the risk of recurrence dramatically in patients who have no evidence of disease. So again, the key question is, is there a clinical trial for my situation?

And then the next question is,

“If I were to enroll in a clinical trial, would I lose my current oncologist?”

And the answer is, no. Certainly at our center, and as far as I know, my colleagues around the country and around the world, encourage the patient’s primary oncologist or current oncologist to stay in the picture. I think it’s very, very important to do that. There’s a connection with that oncologist and that should be preserved. There are now very easy ways to communicate. Multiple different electronic formats. In fact, electronic medical records are often shared directly with different centers. And so personally, and I think the pervasive feeling is that, not only should the patient not lose their current oncologist, but there are concerted efforts to make sure that that individual stays involved. And that truly, at the end of the day, it serves the patients best and is in everybody’s best interest.

So, I think that’s all the time we have. Thank you again for tuning in. And thank you so much for the questions. Again, you’ll have an opportunity to view this on CRI’s YouTube channel, if you want to review any of it. And I’ll also say that we have a patient panel coming up to talk about clinical trials, and I’ll encourage you to tune into that and really get the firsthand patient perspective around participating in clinical trials. Thank you again very much.

Tamron Hall: Dr. Cohen, thank you for that informative presentation. We’re looking forward to hearing you continue the conversation during our immunotherapy patient perspectives panel. That’s coming up next. During this panel, CRI ImmunoAdvocates will share their own personal experiences finding and participating in immunotherapy clinical trials.

We’re going to take a short break before jumping into the panel. If you haven’t already, now’s a good time to set up your confidential, one-on-one consultation with one of CRI’s clinical trial navigators. To schedule your consultation, please email us at patients@cancerresearch.org. We also encourage you to explore resources from our partners during the break. The CRI Resource Guide, which Dr. Cohen mentioned, includes excellent information from sponsors, host institutions, educational partners, and more. We’ll be right back.

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