What is a Clinical Trial Really?

Busting Top Myths About Cancer Clinical Trials

There are so many myths surrounding clinical trials. Many question, “Will I get a placebo? What is the cost of a clinical trial?” To bring some clarity to an often confusing, myth-riddled topic, The Patient Story and The Leukemia & Lymphoma Society (LLS) have teamed up to discuss what a clinical trial is, the phases of a clinical trial, and how to figure out the logistics of paperwork, tests/scans, and finances.

The Leukemia & Lymphoma Society (LLS) is a global leader in the fight against cancer. LLS funds lifesaving blood cancer research around the world, provides free information and support services, and is the voice for all blood cancer patients seeking access to quality, affordable, coordinated care.

The Clinical Trial Support Center (CTSC) is a free service provided by the LLS to help patients find clinical trials, find financial support and to overcome barriers.

In this conversation, Domenica, a cancer survivor who has participated in clinical trials, opens up about her experience, her fears and concerns, and explains how it helped save her life.

She’s joined by Crissy Kus, a CTSC Nurse Navigator, who worked side by side with Domenica to find and join clinical trials, and CTSC Director Leah Szumita, an expert in clinical trials.

Thank you to Crissy, Domenica, and Leah for sharing your stories and expertise!

This story is adapted from a webinar held on November 9, 2022. A copy of the slideshow presented is available at the end of the article.

This interview has been edited for clarity. This is not medical advice. Please consult with your healthcare provider for treatment decisions.

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Then came one cancer after the other. I worked through those years and treatments, but in 2017, [I] began very, very intense treatments. I had different cancers and [went through] not only chemo but also radiation. [At that point] I couldn’t do it anymore. I just concentrated [on] getting cured, to try to find the cure and to be strong. That is when I decided to leave everything and just [began] to fight.

Clinical Trial Information

Domenica, how did you learn about clinical trials?

Domenica: In my case, my doctor is the one [who brought it up]. I knew about clinical trials, but I didn’t think I was going to be a candidate or that I was going to participate in a clinical trial. I moved from Mount Sinai Medical Center, and the doctor told me, “Listen, you have to go to Sylvester. I’m going to introduce you to a doctor, because they have lots of clinical trials. They have another kind of treatment that we don’t have.” 

Leah, what top concerns do you hear from patients?

What happens is sometimes in later-phase clinical trials, there may be a placebo used, but it will always be in combination with whatever is considered the best approved therapy. Another misconception is when clinical trials are talked about, patients sometimes assume that must mean there is no hope for them. 

There are very strict inclusion/exclusion criteria for clinical trials that involve prior lines of therapy. Again, the theme here is that cancer clinical trial participation is really the key step in advancing treatment, and it’s how we’re going to help bring treatments that work for people to the rest of the population. We really want the people who are participating in the trial to be representative of our diverse population. There are lots of really important aspects of increasing awareness.

Leah, what are the phases of a clinical trial?

Leah: It’s a rigorous process. What’s important to understand is that any therapy that’s approved today, whether it’s chemotherapy or a different cancer therapy or even something over the counter that you can go pick up at CVS and Walgreens, at one point [it] was in a clinical trial. 

Before a clinical trial even starts, the research begins in the lab setting. Researchers take either a new treatment, or maybe it’s a combination of drugs that have never been put together before, and they test it in either Petri dish or animals to really see if that is safe and promising in that setting. 

If it is, it can go through the very arduous process of becoming a formal clinical trial. The first phase of clinical trial, a phase 1, is considered first in human. It’s a very small number of patients, usually around 30. The goal of a phase 1 clinical trial is to determine what is the optimal dose, the highest dose with the least amount of side effects. Within that small group of patients, researchers give a group of patients a certain dose, and then if that is well tolerated, [they] give a different group of patients a higher dose and keep doing that until they determine what that optimal dose is. 

After they’ve determined that, it can move into a phase 2 clinical trial. This phase has slightly more patients, somewhere around 100 or so. At this point, researchers say, “Okay, we have this new treatment that is safe, but does it actually work the way we had hoped?” Every clinical trial is set up differently in terms of what outcome measures it’s striving to meet.

It might be overall survival. It may be complete remission. It may be managing side effects or improving quality of life. Researchers are going to take this new optimal dose and give it to these patients to see if they can meet their outcomes. If they do, then that clinical trial can move on to a phase 3. 

There are many more phase 1 and phase 2 clinical trials than there are phase 3 for a couple of reasons. First, 20% of clinical trials unfortunately closed because they never had enough patients enroll. But then there are certain trials that closed because they didn’t determine that optimal dose, or they didn’t meet their outcome measures. 

If a clinical trial does make it through those first 2 phases, it can go into a phase 3 clinical trial, which is where there are 2 groups of patients. The first group gets whatever is this new treatment, and then the other group of patients gets whatever is considered the best approved therapy. 

At this point, researchers want to know, “Okay, is our new treatment as good, if not better, than what’s considered the gold standard or the approved therapy?” If it is, it can then pursue FDA approval.

Phase 4 trials are when something has gone through the prior steps and becomes FDA approved. There can be a more long-term analysis of side effects and effectiveness, and that would be considered a phase 4 trial.

Domenica, how did your doctors work together as a team?

Domenica: Something I didn’t mention before, [is getting a] second opinion. I think it’s very important because when you have this kind of cancer, if it’s so rare, it’s always good to have a second opinion to balance and see what’s going on in different centers. I have another doctor also in Memorial Sloan Kettering and he’s great, too.

Luckily, all the treatments we’ve been doing in Sylvester, they [all] agree. They always talk to each other and they communicate. They work as a team. That, I think, is super important for the patient.

At the beginning, when I was thinking about a second opinion, I said, “Oh my God, the doctor is going to be offended. I don’t know if I can do this.” But I said, “Well, listen, it’s my life.” 

So I spoke to him. He told me, “Please, go ahead. If I was in your side, I would do exactly the same.” That kind of support of the doctors is so important for the patient — that you feel comfortable not only with your doctor, but in this case also having a second opinion.

I want to point out [that] something I hear from a lot of patients is, “I don’t know if I want to send this trial search to my doctor. I don’t know if I want to share with them I’m looking elsewhere, or I’m scared to ask my doctor for a second opinion at another center.” 

Clinical trial paperwork

Domenica: It was overwhelming at the beginning. The paperwork, as you said, [it’s thick]. To tell you the truth, I didn’t read the whole thing. I kind of went through [it], but I didn’t have [any] other option. I wanted to get into this clinical trial, so I signed the papers.

Crissy: One thing I always did when I was helping consent patients to clinical trials was, I always gave them the paperwork beforehand any time it was possible. Certainly, there are instances where a patient comes in, and you’re consenting them the day you found out that they progressed or they’re diagnosed.

However, in the majority of instances, we knew about a patient potentially coming in for a consult for a clinical trial, or we were switching gears and treatment. The day or two leading up to their visit, I would send them a copy of the consent. I always advise, “Read this over. Bring your highlighter. Write down questions. A lot of this is going to feel like there’s medical terminology, and it’s too much to understand. Highlight that, circle it, ask. Come with your questions.” Ask the question, “Can I get a copy of this before I sign it, and look it over?”

The other thing I stress to patients is while that is a very daunting and intimidating form, you can change your mind about participating at any time. Whether you sign the document there with your physician [or] you walk out of the clinic and say, “Oh, I change my mind. I don’t want to do all of that.”

You can change your mind at any point. Like I said, immediately after the visit, a week after the visit, 6 months, a year later. You can change your mind about participation in a clinical trial at any time. 

The third big thing I like to advise patients to do is take someone with you to that visit. If it’s the visit to discuss the clinical trial, if it’s the visit to consent for the clinical trial, bring someone with you because you as the patient are going to be receiving so much information that you’re almost always going to walk out of that visit like, “Oh, I forgot to ask this, this, and this that I wanted to ask.” 

If you bring someone with you, they know those questions you wanted to ask. They’re at the top of their mind and they bring them up. They’re also really good note takers. They might hear something you didn’t hear.

What kinds of treatments, tests and scans happen during the clinical trial?

Domenica: It’s overwhelming because there are so many tests involved. Of course, the typical blood test with all the specifics and PET-CT scans. You go through a bone marrow biopsy. I want to tell you something very interesting, because in the second clinical trial, they did a bone marrow biopsy and they didn’t find the Richter [transformation]. 

Another reason they do this is so every single patient who’s on that clinical trial is worked up in the same exact way. [That way,] you’re comparing apples to apples and saying every patient got the same workup, the same treatment, [and] the same management on the clinical trial. 

Travel and logistics for a clinical trial

Leah: Oftentimes, a clinical trial will take someone away from home frequently or for an extended period of time. Most clinical trials are happening in the large academic centers. For folks who don’t live in those areas, you’re talking about a lot of logistics to figure out. 

I tell people all the time, “Wanting to enroll in a clinical trial and actually enrolling is not a straight path.” There are just so many bumps in the road, and these logistics and finances are two huge bumps in the road. When we talk about the finances related to clinical trials, there’s really three buckets of cost. 

The first bucket of cost is whatever is being studied, so either a new drug, a combination of drugs, a transplant or a CAR-T therapy. That new treatment being studied is typically covered. The cost of that is covered by whoever’s sponsoring the trial

Then you have the second bucket of cost, which is all the other healthcare-related costs — the scans, the bone marrow biopsies, labs, IV fluids or antibiotics when needed — need to either be billed to insurance or paid for out-of-pocket, which can be a significant cost.

The third bucket of cost are all of the other expenses related to participation: travel, airfare, carfare, gas, food, lodging for you and for a caregiver. The majority of that will be out-of-pocket expense. One of the questions we arm our patients with is, to go back to the study team and ask if the sponsor or the site has any money to help support covering for food, lodging, travel, etc. 

What we have found is that oftentimes it takes building a patchwork quilt of resources to get people to a point where they can participate in that clinical trial. At LLS, we have some really incredible financial support programs for patients. We also look outside at other advocacy organizations to really try to build together a plan to make it possible. A challenge is certainly when patients don’t have health insurance. Many times a clinical trial, unfortunately, is not an option for the reasons that I mentioned.

What I want to also emphasize is that a clinical trial is not for everyone, for a multitude of different reasons. But if someone comes to our department interested in learning more and through that process, there’s a different type of treatment that is in their next best interest, whether it’s pursuing standard of care confidently or getting a medication through off-label or compassionate use, that nurse navigator is there to help you overcome whatever barriers there are to that treatment. 

As nurses, we can be very savvy. It’s a little bit of detective work sometimes trying to piece together a plan to help somebody get to that optimal treatment, but this team is so able and ready to do that.

One thing that is very important that I also like to address is you always have to be ahead of the game. Don’t stay with this clinical trial. My husband and I used to call Crissy and say, “Okay, Crissy, we’re here, but what could be next?” Because you don’t know if it’s going to work. You don’t know how long it’s going to work. You always want to be prepared. Crissy is like a guardian angel because she does everything and makes finding the new clinical trial much easier. 

They had a lot of difficulty looking for what trials their patients might be eligible for on that website. Don’t feel down about yourself if you’re having a hard time navigating that. That’s really what our team is here to help patients do. [It’s] to not have to navigate that process on their own and everything else that comes with exploring clinical trials [and] participating in clinical trials

Up until just a few years ago, our team was actually using clinicaltrials.gov to do our personalized searches for patients. It was felt that it was a tedious process that could definitely be streamlined and improved and so LLS poured a lot of resources into creating a proprietary database that only our team has access to. 

Domenica, you’re headed for another clinical trial

Domenica: Yes. I was lucky to find another clinical trial that the doctor introduced me to. [I’m] going to start the tests and everything maybe in a couple of weeks. I hope, it’s a successful clinical trial. 

When we look at just the financial aspect of it, if someone does not have health insurance coverage, whether it’s commercial insurance or Medicare or Medicaid, the cost of the clinical trial will be out-of-pocket. We’re talking hundreds of thousands of dollars for the majority of clinical trials. 

There are several healthcare institutions in the United States that do provide care for clinical trials, regardless of insurance coverage. That would be the National Institutes of Health in Bethesda, Maryland, and St Jude’s for children. They only offer certain clinical trials. It can be challenging to also qualify for those clinical trials. By and large, for patients to come to the United States to participate in a clinical trial, it would be significantly expensive.

Q&A: How has the pandemic affected clinical trial administration?

Leah: One of the realities of COVID, and we’re still in this ongoing state of COVID, is that for many blood cancer patients, they actually have worse outcomes with COVID. There needs to be lots of provisions in place for these patients to safely travel. 

First, I would encourage anybody to talk to their healthcare provider about boosters and COVID vaccines, because that’s a very important thing. We do know many of these folks are at increased risk with traveling. What we are trying to do is help advocate both in the policy space and when we’re meeting with sponsors to try to bring some of that care in a clinical trial closer to the patient. 

One thing we did see in light of COVID is that some of these consults can be done virtually. That’s a great question to ask right from the start. Can some of the visits be done virtually? That would be a great option as well. 

The other reality of COVID is that everything is that much more expensive. All the barriers to clinical trials that existed before COVID are still here. They’re just worse. It really takes that much more effort to try to get the resources to help people safely participate in a clinical trial.

Q&A: During the clinical, does the patient continue with regular visits with his or her oncologist?

Crissy: Anything that’s considered study-specific has to be done at the study site. If there’s study-specific scans, bone marrow biopsies, labs, something like that that needs to be drawn, or even a physical exam to be done with the physician, that has to take place at the trial site. 

That’s something that is communicated up front when discussing the clinical trial. Your primary physician at your local oncology clinic is involved still and can see you in between those study visits, but anything that’s study-specific has to be done at the trial site.

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Webinar Slideshow

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