Clinical trials are essential to bringing promising new therapies to patients, often for the first time or in new combinations with other treatments. What is a clinical trial? What are common misconceptions about clinical trials? How can you access and enroll in a cancer immunotherapy clinical trial? How has the COVID-19 pandemic changed patient participation in cancer clinical trials? These are just few of the questions that Dr. Kunle Odunsi, director of the University of Chicago Medicine Comprehensive Cancer Center, will address during this informative and myth-busting session. Following his talk, you’ll have an opportunity to ask your questions about clinical trials during a live Q&A session.
Tamron Hall: Now, let’s learn about clinical trials. In order for any treatment to get approved, they must first undergo extensive testing in clinical trials. Trials help us understand whether a new treatment works better than another. They also offer other options to patients, and they can be important part of the treatment journey. Here with us today to explain what clinical trials are and why patients explore them, is Dr. Kunle Odunsi, who is director of the University of Chicago Medicine Comprehensive Cancer Center, and Dean of Oncology at the University of Chicago’s Biological Services Division. He’s an associate director of CRI Scientific Advisory Council. Dr. Odunsi works on the front lines of clinical discovery, and he’s here to tell all of us what clinical trials are and what patients need to know when considering a trial. Dr. Odunsi, thank you so much for joining us. And, like everyone attending, I look forward to hearing what you have to say today.
Dr. Kunle Odunsi: Thank you so much, Tamron, for the introduction. I’m very excited to be here to talk about clinical trials today. Clinical trials are very critical with regards to how to bring new therapies to the clinic. They are designed to test new ways to prevent, find, and treat disease. Many times, the clinical trials are helping us to make sure that new treatments are safe and effective, and that these new treatments, based on the latest scientific knowledge, can help not only to achieve remission, but sometimes potentially to think about cures.
So clinical trials are research studies that involve people. They are typically designed to answer specific questions: “Is the treatment safe? Is it effective?”
The questions can be about existing treatments already where we have new questions, or can be about a completely new type of therapy. But the overall goal is to improve treatment approaches for cancer, as well as improve quality of life for patients with disease.
When you think about clinical trials, what are the phases of clinical trials? I’m sure many in the audience have heard about phase one, phase two, phase three clinical trials. So what are we trying to accomplish in a phase one clinical trial? We are simply trying to accomplish and answer the simple question: Is this treatment safe, especially when you are putting a new drug or a new immunotherapy in a patient for the very first time? This is what I call first in human trials, or sometimes it’s a new combination of existing drugs that you are testing for the first time. So one of the principles is to make sure that, above all, we do no harm. So the first question is, “Is the treatment safe?” But I have to point out that even for phase one trials, based on the latest and best scientific evidence, some patients can actually derive benefits beyond just answering the question of treatment safety. Many phase one trials have led to patients experiencing durable remissions or even killers of their disease at the at the level of phase one. But the primary question is: “Is the treatment safe?”
So. If a treatment passes phase one, it moves on to a phase two clinical trial. And here now we’re really beginning to hone in on the question, “Does the treatment work?” As you can see, for phase one patients, you need a relatively smaller size of patient numbers between 20 and 100. When you get to phase two, and you really want to answer the question “does the treatment work?”, it’s going to be important to include a larger number of patients, typically in the range of hundreds of patients. And finally, we move on to phase three clinical trials. Where, in fact, the question now is, “does the new trend work better than existing therapies?” So you are comparing the current therapy, what is considered standard therapy, with the new treatment you randomized into patients, into the two groups and asking the question, “which one works better?”
So there are a number of clinical trials that have taken place over the last several years that have led to FDA approval of many immunotherapies. Again, I’m sure the audience is familiar with the process of FDA approval, given the recent COVID pandemic, where a number of vaccines were taken through the FDA approval process. So this process is not just for the COVID virus, for the Coronavirus. This is the standard process for all approvals where investigational agents’ drugs have to undergo phase one, phase two and phase three testing. Look at the number of approvals for immunotherapies over the last several years. Some of them are approvals in cancers, male cancers, such as prostate, approvals in breast cancer, approval in cancer of the cervix, small cell lung cancer. Almost every organ system in the body. Some of the missing ones from this list, as you can see, include pancreatic cancers as well as ovarian cancers. So this is a promising list of different cancer types where different forms of immunotherapies are effective, but there is work to be done in terms of improving the efficacy for these different cancer types, as well as some of the more difficult cancers to treat, such as pancreas and ovarian. So there is work to be done, but this is an impressive list of what immunotherapy can do.
So there are a number of misconceptions about clinical trials, and I would like to address them. So, misconception number one: this is a myth where some people say, “I might only get placebo or a sugar pill instead of treatment.” But in fact, the real fact is that placebos are rarely used in clinical trials nowadays, and they are never given in the absence of some form of treatment. This is the fact, so it is a misconception that you are getting you’re going to be getting placebo. It’s important, of course, to ask questions, and we’ll talk about that in a minute to ask questions about the clinical trial and make sure you are not getting placebo. But really, placebos are rarely used in present day clinical trials.
Another misconception, another myth, is that clinical trials are only for people who have run out of treatment options as a last resort. The fact is that clinical trials are, in fact, designed for people with cancer of all types, all stages, all time points, whether it’s new diagnoses or whether it’s later diagnosis. There are typically clinical trials because the field is constantly looking for a way to come up with better treatments. So there are clinical trials for all stages.
Another misconception is that I need to travel to a large hospital or cancer center to participate in a clinical trial. That is a myth. The fact is that trials can take place at local hospitals can also take place at the large cancer centers and doctor’s offices in all parts of the country in both urban and rural areas. It is important to ask questions about whether clinical trials are available. But again, nowadays clinical trials are available in many institutions across the country.
Another myth is that my health insurance doesn’t cover the cost of care in the clinical. The fact is that doctor visits, hospital stays, and any testing procedures can actually be covered by your insurance. The research components of a clinical trial are typically covered by the trial sponsor. So the question of the type of health insurance should really not be a barrier to participating in a clinical trial.
Then the other misconception, a myth, is that if I sign a consent form, it locks me in sustaining a trial. The fact is that you have absolute authority over what to do. You have autonomy over what to do. You are free to change your mind for any reason about participating in a clinical trial any time before or during the trial. For that matter, if you have enrolled in a trial, you can change your mind at any time so you have absolute control. It doesn’t lock you into anything.
Another myth is that I would I would be made to feel like a guinea pig experiment. The fact is this is not true. The fact is that major, if you saw the trial participants across the country, or even beyond the United States, you’re going to find that many trial participants say that they were treated with dignity and respect and predominantly report that they’ve had a positive experience in a clinical trial.
Clinical trials are not safe. That’s a misconception. The fact is that clinical trials undergo very rigorous safeguards at the level of the FDA. We talked about the FDA approval process. There are additional layers beyond the FDA. There are there are boards that are called institutional review board that review protocols, clinical protocols, clinical trials before they can be deployed to treat patients. There are also data and safety monitoring boards. There’s an informed consent process that ensures that the patient rights and safety are protected. So clinical trials are safe because of all of these safety measures that have been put in place right from the level of the FDA and to the level of the institution where the clinical trial is taking place.
Let me just highlight a couple of examples of clinical trials that have made a tremendous impact. The first one that I want to highlight is a clinical trial of a checkpoint inhibitor that looks at adults and children with advanced solid cancers with a high mutational burden. What is a mutational burden? Cancers tend to have genetic mutations. It turns out that these genetic mutations that define cancers also provide a signal to the immune system that allows those concepts to respond very well to immunotherapy. So this was shown in a clinical trial where regardless of cancer type, whether it’s lung or ovarian or kidney or bladder cancers, these patients were in a clinical trial testing a form of immunotherapy, an immune checkpoint inhibitor, to ask the question, “if we take patients with high mutation burden, will they respond very well to immunotherapy?” The answer was yes, and consequently, this approach was approved by the FDA as now standard of care. Another example is a recent example of the combination of a checkpoint inhibitor with standard chemotherapy before surgery, and a single agent after surgery, a very striking example, in patients with triple negative breast cancer. Again, the results were positive, and this led to approval by the FDA. If the results were positive compared with standard of care, compared with what we would normally do for triple negative breast cancer up until that point. So clinical trials help us define new treatment approaches that are effective and that have the potential for providing long-lasting remissions.
I want to address certain aspects of when you are contemplating enrolling in a clinical trial. The first point I want to make is be bold in asking for details. This is your treatment plan. It’s important for you to ask questions, ask for details, and again, I talked about the myth of whether or not there’s going to be placebo in the in the in the clinical trial. Typically, there is none, but that’s a good question to ask. Be bold in asking for details because this is your treatment plan.
What kind of questions can you ask? These are listed on this slide, whereby you asking, “What is the purpose of the trial? How long will I be on the trial? What are some of the risks and benefits? What can I expect? What are the alternatives? How are you going to monitor me during this trial? What kind of safeguards are in place? If there’s a need to withdraw from the study, how does this happen?” So those are important questions to ensure sure you have all the facts before and during a clinical trial.
How do you get on a clinical trial? The first is ask your doctor if your doctor has access to clinical trials. Obviously, it should be very clear the doctor will present it to you. If not, the doctor may refer you to another physician, or you yourself may seek out a second opinion. That’s how you get to a clinical trial. You can also navigate the system in different ways, for example, by contacting a patient advocacy organization. A key example is the Cancer Research Institute that has been at the forefront of pioneering, of leadership in the field of cancer immunotherapy. So the Cancer Research Institute has a clinical trial navigation program that I think is absolutely terrific to help navigate the Information surrounding how best to access clinical trials. Then the other way really is to search online. You can you can go again to cancerresearch.org website or another site, clinicaltrials.gov. Those websites are useful. The information they provide can be quite a lot, and therefore, I think getting the help and assistance from a clinical navigation program helps to streamline the information that you are looking for.
So thank you very much for your attention. And at this point, I’m going to see if there are questions. Please feel free to put in your questions at this time. Let’s see if there are any questions. Yes, there are. I’ll be taking these live questions. Continue to submit your questions. These are some of the questions that are coming through.
One question I think I already addressed: “Does a doctor have to make a referral for you to join a clinical trial?” Not necessarily. You can the doctor make a referral? You can also seek information from a clinical trial navigation program, such as the one offered by CRI. Or, you can seek for a second opinion. You can go on the internet, clinicaltrials.gov. We covered that in my presentation.
The next question is, “What is next generation sequencing and how does it relate to immunotherapy?” That’s a great question. One of the clinical trial examples that I showed you talked about how there’s a relationship between the tumor mutation burden. It’s also abbreviated as TMB. Tumor mutation burden causes cancers to have a different appearance from our normal cells. So when you have when the cancer cell has a lot of mutation, then it is significantly different from the normal cells, the normal tissue. Therefore, the immune system begins to feel that this is different. This doesn’t belong. Almost like almost like an infection begins to say “this doesn’t belong here, this is different from the normal stuff.” Therefore, that sends a signal to the immune system and therefore those patients with high mutation burden are more likely to respond to immunotherapy because their immune system is primed and ready to go. So if you then give immunotherapy to further activate the immune system, then you are likely to get better results. So next generation sequencing allow for the measurement of the tumor mutation burden, as well as some other measurements. So that’s the relationship.
The next question here is, “I’m a four-year cancer survivor and I am interested in being part of a clinical research and trial design team. As a cancer survivor, how can I get involved in improving clinical trial design for others?” That is an absolutely excellent question. We’re always looking for individuals like yourself who are cancer survivors who have the experience, who have been in the trenches of not only being diagnosed, but undergoing treatments because those experiences are unique. They can help in how we think about clinical research and clinical trial design. So there are a number of patient advocacy groups that you can participate in. Again, I would encourage you to contact the Cancer Research Institute as well. We’re always looking for cancer patient advocates to help in how we think about clinical trial design from the patient perspective. So, for example, a clinical trial or investigator might not even consider the time you know the common. Sometimes some treatments require coming back repetitively multiple times to the hospital that that raises issues of transportation time, commitment caregivers. So I think a cancer survivor who has this, you know, this unique perspective really can play a role in helping us design better clinical research and better clinical trials. So thank you for that question.
Next question is: “How do you approach clinical trials for cancers that are rare? What if there are not enough people with the same cancer to enroll in a trial?” That’s also a very good question for cancers that are rare. Some of the clinical trials strategy has often involved what we call cooperative groups. It requires collaboration. Some cancers are so rare that a single center is single institution, may not see many of such cancers and therefore may not be able to conduct effective care. If you recall from my slide, phase one clinical trial requires tens of patients. Face Phase two clinical trials may require up to one hundred patients. Phase three clinical trials requires hundreds, sometimes up to a thousand patients. So for rare cancers, first of all, we lower the numbers that are necessary to demonstrate efficacy. And second of all, it requires collaboration, so multiple institutions coming together to conduct these studies. In the United States, there are cooperative groups. So, for example, pediatric trials. Fortunately, pediatric cancers are not as frequent as adult cancers. So there’s a children’s oncology group that is the national. There are the national cooperative groups as some of the rare cancers can be tested in a collaborative fashion.
Then secondly, of the question is, “What if there are not enough people with the same cancer to enroll in the trial?” Occasionally, there is a different pathway that the FDA allows, which is a single patient. Clinical trials, which will use only occasionally these are typically compassionate use clinical trials that they are not frequently used, but they may be necessary sometimes if there’s a rare cancer. As a treatment that is in a clinical trial, that will we really need to use for a patient with a with a with a rare cancer.
The next question says, “I have had tumor genome testing. Will this hurt my chance of getting into an immunotherapy clinical trial?” The short answer is it should not hurt your chances. Actually, the short answer is no. It should not hurt your chances of getting into an immunotherapy clinical trial. If anything, it provides additional information about the type, the nature of the cancer, the nature of the tumor, and begins to provide information of whether this is a tumor that is mutation high, or tumor mutation low, and other parameters that may actually allow the selection of the type of clinical trial and that you should be undergoing.
The next question…there are really very good questions is here, please keep, you know, bringing in these questions.
Another question is, “At what point in my treatment should start looking for a clinical trial?” I would say right from the get-go, begin asking questions from your physicians, whether or not there are clinical trials at that point, whether at the time of diagnosis or somewhere down the line.
“How do clinical trials need to go before a drug can be approved by the FDA?” I think I showed in the presentation one of the slides how clinical trials need to go from phase one, to phase two, to phase three clinical trials. Typically, it goes up to phase three before it can be approved by the FDA. But there are additional mechanisms which FDA can give some accelerated approvals even without a phase three clinical trial.
“What efforts have been made to increase the numbers of people of color in upcoming clinical trials?” That is a very important question. One of the challenges that face us as a nation is area of health care disparities, and this extends to cancer health care disparities. So many institutions in the United States, especially the NCI designated comprehensive cancer centers, are making tremendous efforts to make sure that we increase the numbers of people of color, underrepresented minorities in clinical trials. So I’ll give you an example: multiple myeloma is a disease that predominantly affects people of color. I think about 20 percent of multiple myeloma patients are African-Americans, people of color. If you consider multiple myeloma clinical trials, only 4.5 percent of African- Americans are enrolled in such clinical trials. It is very clear that sometimes the safety efficacy of certain drugs could be different depending on ethnic group or racial group. So it’s very important for us to continue to increase efforts, to increase participation of minority populations in our clinical trials. I know if I felt that this effort is ongoing at many cancer centers across the United States.
As a similar question about access to trials, “How do you think we can improve accessibility of clinical trials for patients who live far away from cancer research centers?” That is also a good question for rural populations in the United States and other places. Again, this is something that a lot of people are focused on trying to make sure that patients who live far away from major cancer centers have access. This is done via a network of the cancer centers, or even some of the local hospitals have their clinical trials as well.
Another question: “I currently have no evidence of disease. Can I still enroll in a clinical trial for immunotherapy? If not, what do you advise one to be ready if my cancer returns?” The short answer is again to engage with patient navigators. There’s a navigation system within the CRI, and they will be able to help to determine whether there are any clinical trials that could be suitable for your state of remission at the present time.
“In the future, do you think that patients will be able to receive immunotherapy at home while on a clinical trial?” I would think so because we are rapidly, I mean, the COVID pandemic taught us many lessons about things that we can probably do remotely, more things that we can do remotely that we used to think can only be done in the hospital. So I think that more and more care will shift from hospital settings to the home or community settings.
This is the last question: “I had to leave an immunotherapy clinical trial because of a side effect. Can I still get access to the drug of the trial?” I think it’s important to discuss this with your physician and discuss whether it’s appropriate to get the drug and whether or not there can be access to the drug.
With that, I think our time is up. Again, thank you very much for your attention, and I hope that you continue to engage. If you are a cancer patient, think about clinical trials that can be truly transformative in terms of helping the cancer journey, as well as helping future patients with cancer to get better results. Thank you once again.