Stepping up for Science
By Martha Nolan McKenzie
Robin Roberts was able to return to her host spot on Good Morning America.
Melissa Etheridge was able to record more songs. Brandon Davis was able to go back to playing professional ice hockey. All these feats were made possible because somewhere, at some time, a patient enrolled in a clinical trial and received an experimental treatment for the first time.
"The many successful treatments we have for cancer today are here because someone was willing to try a new drug in a trial," says R. Donald Harvey, director of the Winship Phase I Clinical Trials Section. "Without clinical trials, we would not be able to move medicine forward."
A clinical trial is a research study that tests new ways to prevent, diagnose or treat disease. Trials investigate promising new drugs, drug combinations, new approaches to surgery or radiation therapy as well as novel treatments such as immune or gene therapies. New treatments make it into clinical trials only after they have spent years undergoing development in the lab and testing in animals. Testing in humans is conducted in three phases (see sidebar on page 13) over many years before a new treatment can be approved by the U.S. Food and Drug Administration (FDA).
Pulling together everything involved in running a clinical trial takes a team approach. "An entire group needs to work together to run a trial, including basic scientists, clinician scientists, research coordinators, research nurses, pharmacists, and regulatory specialists," says Bassel F. El-Rayes, associate director for clinical research and director of the gastrointestinal oncology program at Winship. "That’s what a cancer center like Winship does. It brings all these people together under one umbrella."
It’s something Winship does quite well. Since 2007, a whopping 75 percent of all new FDA approved cancer drugs have been tested through a Winship clinical trial. Fueled by the strong scientific research base at Winship and Emory University School of Medicine, 40 percent of all the trials here are investigator initiated. That means the drug or treatment being studied grew from the basic research of a Winship investigator. "Our investigators prefer to write their own studies and to be on the forefront of research," says Harvey. "Having investigator-initiated studies is a focus of our research mission."
Winship’s clinical trials program is growing steadily. In 2013, 760 patients were enrolled in 250 Winship clinical trials. This year, investigators hope to enroll over 800 patients. And Winship has been selected as a Lead Academic Participating Site for the National Cancer Institute’s (NCI) new National Clinical Trials Network (NCTN). The NCTN will serve as NCI’s primary infrastructure to conduct Phase II and III cancer clinical trials. NCTN clinical trials will enroll over 17,000 patients per year with a variety of cancer types and from diverse backgrounds.
The clinical trial work done at Winship is critical to advance the treatment of cancer. "There are very, very few diseases out there for which we feel we have the best treatment possible," says El-Rayes. "There is always room for improvement, especially in cancer treatments. Clinical trials are the way for us to either improve outcomes or produce the same outcomes with fewer side effects."
Despite the importance of clinical trials, only about 5 percent of adults with cancer enroll. Why? Reasons vary, including lack of knowledge of trials, access to care, feeling it’s a last resort, fear of getting a placebo and perception of being a human guinea pig. While participating in a clinical trial may not be the right choice for every patient, it’s critical to make the decision based on facts rather than myths.
The first obstacle – lack of awareness – is easily overcome. It’s true that patients usually are referred to trials by their doctors, but you can ask about trials if your doctor doesn’t bring it up. You can also search for trials yourself at ClinicalTrials.gov, a service of the U.S. National Institutes of Health. There are clinical trials for almost every type of cancer and stage of disease so a little digging might turn up an appropriate trial.
"Do not sign this consent form unless you have had a chance to ask questions and get answers that make sense to you."
–Winship/Emory clinical trials consent form
The feeling that clinical trials are only an option after all other treatments have failed is misplaced. While some people do enroll after other treatment options have been exhausted, others consider trials right from the outset. That’s the decision Cindy Sullivan made. When the Athens woman was diagnosed with multiple myeloma in 2008, a year after her daughter’s birth, she was given two options. She could get standard treatment in Athens, or she could commute to Atlanta to participate in a Winship clinical trial testing a new combination of drugs. "When I heard about the clinical trial, I knew that’s what I wanted to do," says Sullivan, now 46. "I didn’t want to look back and regret that I hadn’t done everything I could."
Fears of getting a placebo are also misguided. In cancer clinical trials, you will either get standard of care – what is generally considered to be the most effective treatment available – or the new treatment being studied. "The only time a placebo is used in a cancer trial is when there is no standard of care," says El-Rayes.
And far from being treated as a guinea pig, clinical trial participants are seen as heroes by the medical team and are given the utmost respect. Indeed, you will likely get more attention from your health care team and more careful monitoring of your condition and the possible side effects of treatment if you take part in a clinical trial. And participation can be empowering, giving you the feeling you are playing an active role in your care and helping others who will come after you.
The opportunity to pay it forward is what motivated Katie Groover to enroll in a clinical trial. Groover was diagnosed with an aggressive form of multiple myeloma in 2011. Her doctor referred her to Sagar Lonial at Winship because she was aware he was involved in many clinical trials. "Dr. Lonial spent an hour and a half with my husband and me explaining about the trial and told us to go home and think it over, but I had pretty much made up my mind before I walked out of the office," says Groover, now 54. "The Lord has been good to me and I see being in a clinical trial as a way to give back. I’d like to think I was able to help advance medicine to find a cure for this cancer."
There are many other things to consider when weighing whether or not to enroll in a trial. You may be getting a treatment that has not been tried in humans before or been used for your type of cancer. That’s a risk that can cut both ways – if the new treatment turns out to be effective, you’d be among the first to receive it and benefit from it. On the other hand, if it turns out to have unanticipated side effects, you could suffer those.
Paul Hansen has experienced both sides of the equation. When Hansen’s non-Hodgkin lymphoma came back in 2010 after two earlier rounds of chemotherapy, he enrolled in a Winship Phase I trial. The treatment was ineffective against his cancer, so he started another chemo regimen that put him in remission. When the cancer returned in 2013, it took the form of very rapidly growing tumors all over his body. He enrolled in another trial, and this one worked like a miracle. "It was just unbelievable," says Hansen, now 62. "You could practically watch the tumors shrinking. I’m in total remission right now."
Phase I trials are testing drugs for which, to date, information on side effects in humans is limited. During the trial, patients are very closely and frequently monitored to ensure safety. Some are checked every 15 minutes while the drug is being administered. While historically, first-in-human Phase I trials have been reported to benefit only about 10 percent of participants, either by eliciting remission or shrinking a tumor, Harvey contends the benefit is understated. "If you go into a trial and your tumor stays the same size rather than shrinks, that’s considered not responding to the treatment," says Harvey. "But I would consider it a win for the patient, particularly if they had very few side effects. It means we’ve stopped the growth of the cancer. If you are feeling well, that’s the beginning of the definition of a chronic disease. If you can take a drug or a combination of drugs that cause very few side effects and keep the cancer at bay, that’s a chronic disease, just like high blood pressure or high cholesterol. And we’re getting there."
Participating in a trial generally gives you access to top cancer doctors and scientists, and your treatment is closely monitored by an entire team. On the other hand, you will likely need to make more frequent and longer visits and submit to more testing. "We ask a lot of our patients, particularly in our Phase I trials," says Harvey. "We ask many times that they come to our center six or seven times in a three to four-week period. We ask that they spend upwards of 10 hours with us so we can give drugs, collect blood samples and assess how they are feeling. We ask that they perhaps drive long distances to Atlanta and maybe stay overnight. Our trial participants are phenomenally courageous and giving of their time."
Cost likely will not be an issue when considering a trial, as long as you have insurance coverage. As a general rule, your insurance will pay for anything that you would have gotten as standard of care, and the trial generally covers all expenses related to the research. "A patient needs to check with his insurance company and find out what will be covered," says Kathleen Rodger, director of the Clinical Trials Office at Winship.
Of course, if you do want to participate in a trial, you must first qualify. Every trial has certain specific conditions that must be met. Eligibility criteria can include treatment history, other medical conditions and type and stage of the disease.
In addition, you need to be in good condition, meaning you are still up and about and able to do most things for yourself. "We want to make sure the trial is safe for the patient," says Rodger. "Trials generally look for people who are healthy enough to tolerate treatment."
And some trials are adding another type of criteria – looking for biomarkers that are believed to predict the likelihood that the drug being tested will be effective on you. "We’ve now added a layer of screening into the trial," says Harvey. "Not only do patients have to be physically fit, they have to be molecularly fit. This is done with the hope that we’ll have more targeted therapies and more personalized approaches."
A personalized approach is exactly what Winship is striving for. Indeed, one of Winship’s distinguishing characteristics is a dedicated Phase I unit. "We not only have a dedicated space, we have dedicated personnel and a dedicated culture," says Harvey. "For example, we draw all the labs here. The physicians come to see the patients here. EKGs are done here. Our goal is to make this a truly patient-centered experience."
It certainly was for Groover. "We called it the VIP room," she says. "I had the same nurses and technicians every time I went, and everything was brought to me."
But perhaps the thing that stands out the most for Winship trial participants is the level of caring they received. "I honestly can’t say enough good things about the people who treated me at Winship," says Sullivan. "I actually became great friends with some of those nurses. They understand you are not a number – you are a person with a life and hopes and dreams. They truly care about you when you are there, and it makes a difference."
What the Phases Mean
Phase I trials study whether a new treatment is safe to use over a range of doses. Sometimes a drug is being used for the first time in humans. The treatment may be given to people with different types of cancers. A Phase I trial is mainly a drug safety study and tends to be small, enrolling around 20 patients.
Phase II trials study how well a treatment works for a certain cancer. These trials may include between 25 and 100 people. After a drug (or procedure) is found to be effective in treating cancer in a Phase II trial, a Phase III trial will study it further.
Phase III trials compare the new drug or procedure to accepted standard treatment to see which works the best. Phase III trials may look at different doses of the same drug, different drug combinations or different sequences of giving drugs. In these trials, people are randomized to get either the new treatment or the standard treatment. Phase III trials are large, enrolling hundreds or sometimes even thousands of participants.