Moving Homegrown Ideas into the Clinic
Bringing new cancer therapies to the broader patient population is a multifaceted process. Whether it’s a new therapy, revised method of surgery or novel combination of the two, it must always be first tested in humans before becoming approved standard of care.
The majority of human trials are conducted by the pharmaceutical industry. Institutions across the United States including The University of Kansas Cancer Center support these clinical trials as patient sites, closely following the pharmaceutical company’s guidelines, administering the treatment and then monitoring the patient. All data is sent to the company for analysis.
Not all clinical trials follow this path: A researcher with an idea can also design and initiate a clinical trial. Called an Investigator-Initiated Trial, or IIT, the idea is born and grown at academic medical institutions like The University of Kansas Cancer Center.
Pharmaceutical clinical trials typically test a new therapy for a specific issue; they do not investigate all potential uses for the new therapy. The goal of an IIT is not always to test a new therapy, but to find new or revised applications for already-approved products. IIT’s expand product knowledge, including safety.
IIT’s are a niche academic area, and it takes a complex support system in order to execute the study conception, quality control and quality assurance, design and data analysis and interpretation.
Qamar Khan, MD, associate professor of medicine, has led 7 breast cancer IITs in his career.
“The National Cancer Institute views IITs as an indicator of cutting-edge research. With an IIT, we come up with the idea, we design the trial and we obtain our own funding,” Khan says. “It is 100% our own.”
Melissa Mitchell, MD, PhD, assistant professor, balances patient care with research. Her interest is in reducing overuse of radiation therapy in certain breast cancer subpopulations.
“When I was in graduate school, I knew I wanted to conduct research and treat patients,” Mitchell says. “When you are in charge of your own clinical trial, you have the opportunity to change standard of care and therefore drastically change the outcome for an entire group of patients – not just the ones who walk through your clinic.”
Observation leads to innovation
For many physician-scientists, inspiration comes from their patients.
“The research questions always come after my interactions with my patients in the clinic. You find the unmet need for that particular situation,” Khan says.
“We wondered if these patients would benefit from treatment before surgery. Then we could study the biology of cancer, allowing us to personalize the treatment to the individual patient,” Khan says.
This thought spurred a small clinical trial testing a combination of 2 therapies in women with ER-positive breast cancer with the hope that they may be able to avoid chemotherapy while still effectively treating the disease.
The trial has revealed encouraging results, and Khan is preparing for the next phase, which will take place at 10 centers across the United States. Siteman Cancer Center, an NCI Comprehensive Cancer Center, will analyze biopsy samples. The University of Kansas Cancer Center will monitor and conduct the trial.
“This next phase is a completely unique model – a large investigator-led, multicenter trial,” Khan says. “A collaboration of so many NCI-designated cancer centers participating in an IIT is unprecedented.”
For Mitchell, it was remarks made by her patients that propelled her toward one of her investigator-initiated trials.
“Some patients are more fearful of radiation than any other component of their cancer care. Several of my patients who had no cancer left after chemotherapy and questioned why they need radiation. It is standard of care to give radiation to anyone with breast cancer undergoing lumpectomy, as we know there is a survival benefit. However, in HER2-positive breast cancer patients, newer targeted agents have drastically improved outcomes, and studies have begun to question whether radiation is actually needed for these patients,” she says.
Mitchell was cautious, but looked closely at the data. She was encouraged by what she saw and consequently initiated a trial that will study the effects of omitting radiation as part of overall therapy.
“This is a first-in-kind trial,” Mitchell says. “No one else is doing this.”
Every clinical trial has a long journey before it makes it to the broader patient population. But The University of Kansas Cancer Center’s curious, passionate investigators are dedicated to developing the latest in cancer care.
“We ask the questions that could lead to the next cutting-edge cancer therapy,” Mitchell says. “Our patients have the opportunity to receive the latest treatment before it’s even available to the broader patient population.”
Bench to Bedside: Clinical Trials
Roy Jensen: Welcome to Bench to Bedside, a weekly series of live conversations about recent advances in cancer from the research bench to treatment at the patient's bedside. I am Dr. Roy Jensen, director of the University of Kansas Cancer Center. My guest today is Dr. Joaquina Baranda, who is a medical oncologist at the University of Kansas Cancer Center. Today, we are talking about clinical trials. Clinical trials are research studies that involve people. Often, a clinical trial is used to learn if a new treatment and/or has less harmful side effects than standard treatments. Clinical trials are one of the final stages of a long research process. The process often begins in a laboratory where scientists first develop and test new ideas.
recording: [crosstalk 00:01:18].
Roy Jensen: Nearly all of the tried-and-true cancer drugs available to you today exist because of the past patients who participated in clinical trials. Dr. Baranda, tell us about your role at the University of Kansas Cancer Center.
Joaquina B.: Yeah. Thanks, Roy. Thank you for the invitation today to be with you. It's an honor. Yes. I'm a medical oncologist and a physician-scientist. Just like some doctors in large academic cancer centers, I get to wear a number of hats in the cancer center. Just to give you an idea of how I spend my week, I have of clinic at our Westwood Cancer Center Campus where I see patients with gastrointestinal cancers, like colon cancer, stomach cancer, esophageal cancer, pancreas cancer. But most of my time is actually spent at our clinical research center down the street on Fairway where I join a team of highly dedicated doctors, nurses, pharmacists, basic scientists with a common mission of taking care of patients on clinical trials in order to improve the outcome of our patients with cancer.
recording: [crosstalk 00:02:48].
Roy Jensen: How do clinical trials actually work?
Joaquina B.: Clinical trials are research studies that are based most of the time on the discoveries in the laboratory. These discoveries are based on the questions we have in the clinic so that if, for instance, we're seeing certain treatments that are not very satisfactory, we go to our basic scientists. They come up with many discoveries in the laboratories with potential to answer some of these questions, such as, "What would be a better treatment for certain cancer?" We don't do clinical trials on all of those discoveries, but we choose discoveries with the highest potential that would result in the greatest impact in the care of our patients. Then a protocol or a treatment plan is written. This is a very well-written document that guides everybody taking care of our patients on clinical trials to make sure that all the precautions are in place, to ensure safety, the highest level of safety that is possible, with the highest potential for it to work against their cancer. Some trials are done in order to prevent cancer or diagnose cancer at an earlier stage, but the majority of our trials I do are mainly on using novel treatments in order to find better approaches to how we treat cancer nowadays. As you know, even if we have major advances now in cancer treatment, we are actually not satisfied yet. We are not there yet because there are still obviously patients who are dying from the cancer. However, in the last decade or two, with better understanding of cancer in its very molecular level, clinical trials have actually improved. In the past, when we talk about phase I clinical trials, we're talking about testing a drug that has a potential to work, but we test it on a large number of patients. Back then, we were looking for very small benefit. Now, because we understand cancer better using information from the laboratory, looking at molecular changes or mutations in the genes, we can now target those changes. Therefore, the drugs we use have higher potential in treating a smaller group of patients, and therefore, early-phase or phase I trials are now done quicker so that drugs become more available to patients with cancer in general faster than usual. So it's very exciting.
Roy Jensen: Yeah. What types of cancer patients are eligible for clinical trials?
Joaquina B.: Again, trials are different. They vary from trial to trial, depending on the goals or objectives of the trial. There is what we call eligibility criteria. That is a list or a guideline, a list what kinds of patients we want to be treated in that clinical trial. It is based on safety, so we would look for patients with specific blood tests that are normal in order to protect those patients who have the potential to, for instance, be affected by a drug that has the potential to affect a certain organ system. But I would say, talk to your doctor, and talk to your research contact in order to find out whether you would be eligible for a certain trial or not.
Roy Jensen: And they can always call the CRC to see we have a trial available, right?
Joaquina B.: Absolutely.
Roy Jensen: At any given time, we have probably around 150 trials that are open, so-called interventional treatment trial. Can you tell us what are the unique aspects about the trials that we offer at the KU Cancer Center?
Joaquina B.: Yeah. The clinical research center is something unique to our cancer center. The vision is so that our patients don't have to travel thousands of miles to get novel treatments. We want to do phase I trials at the CRC in order for our community to have access to these novel agents. To tell you frankly, some of the trials that we participate, we actually have safety calls from investigators throughout the nation from large cancer centers. We share information of observations we have on patients on certain clinical trials. They share their information. There's actually a true exchange of ideas and information that I think leads to patient safety and moving the trials faster with those collaborations. We also have what we call IIT program here where our physician-scientists are able to collaborate with our basic scientists and figure out the best way to do clinical trials so that we can marry the answers from the laboratory to the clinics by performing high-impact clinical trials.
Roy Jensen: In terms of patient benefit, what are the advantages to patients in terms of participating in a clinical trial?
Joaquina B.: These novel treatments that we give in clinical trials are not commercially available. By participating in some of these early-phase clinical trials, the patients are able to access these treatments that we have. As you know, some of the cancers we have do not have standard treatments, or, if they have standard treatments, they are of marginal benefit. Therefore, one benefit is to try a new drug that you cannot otherwise access, but you can access it through a clinical trial. The other is that you are able to exercise your right to choose what kind of treatment you want, how your care would ... you would like it to look like. One major thing is you're actually giving valuable contribution to cancer research by doing that.
Roy Jensen: In terms of misconceptions about clinical trials that you hear out in the community, could you tell us a little bit about some of those issues?
Joaquina B.: Sure. When I talk to patients about participating in clinical trials, one of the questions they have is, "Am I going to get placebo?" Placebo is a sugar pill that does not have any effect or treatment effect. Most trials actually do not have placebo. Most trials, if they have different treatment arms or different assignments of treatment, will have a standard treatment versus a standard treatment plus the new drug or a novel therapy. If there is a placebo arm, you will know if there's a placebo arm. But most of the time, the placebo is combined with a standard of care treatment.
Roy Jensen: If you're just joining us, we're talking about clinical trials. Cameron Poindexter is here in the studio to take your questions. Remember to share this link with people you think may benefit from this discussion and use the hashtag #BenchToBedside. A common concern of patients is that they will stop receiving standard of cancer and only receive the treatment being tested in the clinical trial. Would you address that concern, Dr. Baranda?
Joaquina B.: Yeah. If there is a standard of care for a particular disease or a particular cancer, that standard of care will not be repelled. As I said, most of the time, you will receive the standard of care plus the novel treatment. The other part of this, which is important, the care of our patients, is continuing supportive care, best supportive care. When we do clinical trials, the nurses and the doctors taking care of the patients in clinical trials try everything they can to maximize giving all the supportive measures. Pain management, psychosocial support, nutrition ... Those are quite critical in taking care of patients with cancer in general.
Roy Jensen: One of the things that one of my mentors, David Johnson, taught me is that, even for patients who are receiving standard of care that are on a clinical trial, their outcomes tend to be better than patients getting standard of care that are off of a clinical trial. His theory on that was that patients are being monitored very closely on the trial. They're assured that they always get their drug on time at the right dose, and they're constantly monitoring side effects. Frankly, it's just a higher level of care when you're on a clinical trial, so the patients do better. Do you have any thoughts on that?
Joaquina B.: Yeah, absolutely. I totally agree with that because, just like what I said, these protocols are well written to maximize safety of our patients. Therefore, we do closer monitoring of toxicities, including laboratory tests. One of the things that we tell our patients when they're participating in clinical trial is that you probably will have more frequent visits. You may have more blood tests than you would otherwise get if you were not on a clinical trial. Some patients, however, have concerns that those visits and exams, including CAT scans, may not be covered by their insurance. In fact, most clinical trials are not associated with added out-of-pocket cost because the standard of care procedures, like blood tests and CAT scans, if you were to get that if you were not on a clinical trial, would be covered generally by your insurance. Those that are considered outside the standard of care are actually generally paid for within the clinical trials. I would like to assure patients that, most of the time, that is usually figured out very well by our study teams and our financial counselors.
Roy Jensen: What about safety concerns? How is safety monitored during the clinical trial?
Joaquina B.: Yeah. A lot of these drugs that we use, we have information and knowledge as to what are the likely side effects associated with these drugs. However, because these drugs are being tested in humans not for too long of a time, we do added blood tests and added visits, as I said. In addition to that, it's actually a team effort. The oversight is incredible when you are on a clinical trial. As I said, you are not the only one taking care of patients. It's a team of doctors, study coordinators. Plus, we do have, as I said, safety calls among the network of doctors doing the same clinical trials.
Roy Jensen: How can patients learn more about clinical trial opportunities that may benefit them?
Joaquina B.: Yeah. One one-stop website is the clinicaltrials.gov. Patients can go into that site, and they can find many clinical trials on different kinds of cancer and different places where they can access those. But they can go to our website also, the University of Kansas Cancer Center website. There is a link there where they could clink, and they will find contact information there.
Roy Jensen: If you're just joining us, we're talking about clinical trials. Cameron Poindexter is here in the studio to take your questions. I believe we have might have gotten a question. Cameron?
Cameron P.: Yes, we do. We have a question from Olivia Francos. If a patient may benefit from a clinical trial, do you recommend that most of them get involved in their specific cancer as applicable? Are there any downsides?
Joaquina B.: Thank you for that question, Olivia. The first part of that question is whether they should contact somebody for that specific cancer. The good thing about clinical trial nowadays is that the clinical trials are done in a way that they put the different cohorts that we say, groups of patients, into disease-specific cancers. For instance, we're testing drug X. We would have different groups of patients where some will have non-small cell lung cancer, for instance. Some will have breast cancer in the same clinical trial. That is in an effort to find a signal of how active that treatment is, faster. I would suggest that, even early on, at the time of your diagnosis, you don't have to wait until you have exhaust all the standard treatments available for you. I would say at the time of diagnosis, you should always ask your doctors for available clinical trials for the cancer that you have and perhaps for the molecular changes that your cancer have. The second part of that question is the downside. Whether or not you're in a clinical trial, cancer treatment, unfortunately, has downside. That is these drugs and side effects. However, again, you are very closely monitored. Well, even at the time that these protocols are written, again, they are written in a way to protect the patient. The patient is the center of it all. We want to make sure that the patient is safe and the patient gets benefit from the treatment.
Roy Jensen: You and I got to participate in an event last week that was a celebration of our clinical trials office. We had some very special guests there. Could you tell us a little bit about that event, Dr. Baranda?
Joaquina B.: Yeah. Because of your leadership and the hard work of the people in clinical research center led by Dr. Steve Williamson, we were able to achieve a milestone where we enrolled 100 patients in 2017 in our early-phase program. It's a major milestone because I have been at KU for a long time, and that's the first time that we have seen that number of patients enrolled. We are totally indebted to every patient who participated in the clinical trial. We did have two guest speakers who are patients of ours who described incredible experience they had while they were in the clinical trials. I would suggest that you guys look for those video. I think they may be available. We are just indebted to the patients who participate in these trials.
Roy Jensen: What would you like to say to patients who are considering a clinical trial?
Joaquina B.: Clinical trials are a major tool in the fight against cancer. We're not done with this fight yet. I think we should continue this partnership, and I think we will get there pretty soon where cancer, hopefully, will be a thing of the past.
Roy Jensen: Well, thank you, Dr. Baranda. I just want to again thank our patients that have enrolled in clinical trials at the KU Cancer Center. They are one of our greatest strengths. Frankly, without them, we could not make the progress that we've been making over the last few decades. It wasn't too long ago, back in the 1970s, when the five-year survival rate for cancer was less than 50%. Now, it's nearly 70%. All of that progress is solely attributable, or at least in large part, due to our patients being willing to enroll on clinical trials. Thank you, Dr. Baranda.
Joaquina B.: Thank you.
Roy Jensen: That's it for today. Next week, we will be talking about the fear of cancer recurrence and tips on how to manage that fear. That's right here, next Wednesday, at 10:00 AM. Good day.
Joaquina B.: Thank you.