Debunking the Myths of Clinical Trials

Published in the Summer 2014 issue of LBBC's Newsletter, Insight

Clinical trials, research studies in humans, are the main way new anticancer medicines and prevention and diagnosis techniques are tested and approved for use. Yet the number of adults who join cancer clinical trials is quite low. Concerns about safety and getting the best care, as well as unclear ideas of how research is done, may prevent people from enrolling.

Despite the popular belief that medical research in humans is unsafe or scary, some people find the structured care offered through clinical trials comforting. They also may see benefit in having access to new study treatments to try.

“Joining a clinical trial was the best thing I ever did,” says Fran Kamin, 51, of Lake Worth, Florida. “It’s amazing to me how many misconceptions there are.” Fran took part in BOLERO-3, a study of everolimus (Afinitor) for treating HER2-positive metastatic breast cancer. Researchers found that participants treated with everolimus lived for longer spans of time without the disease growing or spreading.

Deciding whether a clinical trial is right for you is a personal choice, but your healthcare team can help you make an informed decision.

How Trials Work

“Everybody wants the best possible care,” says D. Lawrence Wickerham, MD, associate chairman of the National Surgical Breast and Bowel Project. “Participation in trials is how we ensure that high quality care.”

Before a new therapy or approach reaches the point of being tested in a large group of people, it must go through testing in animals or test tubes and through two rounds of research in small groups of people., A treatment must be found safe and effective in these steps, or phases.

If a treatment is found safe and of benefit through a large phase III trial, the U.S. Food and Drug Administration may grant approval for it to be used outside of trials. The FDA monitors trials and must give researchers permission to move from one phase to the next.

“The reality is that trials are highly regulated, with an institutional review board checking protocol and reviewing participant consent forms before and during the study,” says Dr. Wickerham.

Trial Types

There are four types of trials:

• Interventional trials compare new treatments or therapies with standard therapies
• Prevention trials test methods of preventing cancer from forming or returning. If a trial is studying recurrence, you may be able to participate after you finish treatment
• Diagnostic trials explore whether imaging or other methods help doctors find breast cancer earlier or learn more about the cancer faster
• Follow-up trials monitor people who have used a certain treatment or therapy over a long period to watch for changes in quality of life and side effects.

Trial Phases

New study medicines and treatment techniques go through three phases of testing before they may gain FDA approval. They must be successful in one stage to move to the next. These phases are:

• Phase I. Researchers test a new treatment in a very small group of people to find out how to give the medicine, what kind of side effects it causes, and how safe it is to use. Fewer people are eligible to join phase I trials, and they are not disease-specific.
• Phase II. A slightly larger group of people, all with the same disease, get the study therapy to see how well it treats that disease. Researchers watch for side effects.
• Phase III. Because past findings show a therapy is likely safe and seems to be effective, a very large group of people is recruited so that the new treatment can be compared to standard treatments. The goal is to find out whether the new therapy is as good as, or better than, the one already in use.

Phase III clinical trials are usually randomized, which means a computer assigns participants to each treatment group. Having a computer select the groups gives everyone an equal chance of getting the trial therapy.

One common fear is that in a randomized study a trial participant won’t get the approved treatment for their cancer. Some people believe that if they aren’t given the trial treatment, they won’t receive treatment at all.

During phase III trials studying therapies for active treatment, researchers aren’t allowed to give you no treatment, unless this is the standard of care for your disease. If you aren’t receiving the trial medicine, you’ll get the same treatment you would have had outside of the trial.

Boards and Committees for Protection

One way participant safety during trials is monitored is through institutional review boards, IRBs, teams of doctors, experts, researchers and sometimes community members, who decide whether a trial is safe. The IRB can stop a trial at any time if they feel participants are at risk.

Data monitoring committees serve the same kind of purpose, but are made up mostly of scientists. A data monitoring committee can tell a sponsor to stop a trial for safety reasons or because they feel it won’t lead to a useful result.

Clinical Trials and Participant Safety

Stacy Hansen, 33, of Apopka, Florida, who has triple-negative breast cancer, is participating in a blind prevention trial of NeuVax, a vaccine developed to help prevent HER2-negative breast cancers from returning. In blind trials, neither the doctor nor the participant knows whether the participant is getting the trial medicine or the standard of care.

“It’s a little annoying that it’s blind, but I have a 50 percent chance of being in the group on NeuVax,” she explains. “Without joining the trial, my chance of having the vaccine was zero percent.”

For people with triple-negative disease, clinical trials can offer a less sudden transition out of primary treatment. Unlike hormone-positive cancers, triple-negative cancers do not have post-treatment maintenance therapy. Using a trial medicine may ease the common worry that there’s nothing to protect you from a future recurrence.

“It can be scary as someone with TNBC because once you’re finished with chemotherapy, you’re done. You go from seeing doctors all the time to seeing them once a year. In the trial I see a doctor once a month,” Stacy says.

Informed Consent

Before you join a trial, you must first go through a process of giving informed consent, during which the research team or their coordinators talk with each participant about the details of the trial. You will learn about the benefits and risks of enrolling, financial costs, and how the study will be structured and monitored. In some cases, you may be asked to show the team you understand the information given. You should then be given time to think about whether to enroll.

Barb Young, 47, of Boyertown, Pennsylvania, took this approach before joining NSABP – B-49, a study comparing two different types of chemotherapy for HER2-negative, early-stage breast cancer. Barb has triple-negative breast cancer, which means it’s negative for HER2 as well as estrogen and progesterone receptors.

“My oncologist recommended the trial to me but I didn’t jump right in,” says Barb. “I was worried at first, so I started asking questions. ‘What’s involved? What does joining mean for me and my health? Will I get the best care I can possibly get?’”

The research team and trial nurses took time to help Barb understand the trial before she made a decision.

“The trial nurse sat with me for a good half hour explaining all the details,” she says. “Throughout the trial there was always someone there to guide me and make sure I knew what was happening next.”

Many people report that during a clinical trial, doctors and staff are more involved in care coordination than they might be during regular treatment. In order for the data collected to be as useful as possible, each person’s care must be handled almost exactly the same, so personal support staff — like trial nurses — are an important part of collecting all of the information needed for the study researchers to carefully analyze.

Dr. Wickerham says the movement toward having strong staff support for participants is one way that clinical trials are becoming more sensitive to participants’ needs.

“Oncology has a very good reputation for supporting trials,” says Wickerham. “The trial process is part of the residency and fellowship phases of oncology education.”

Accessing Clinical Trials

Clinical trials aren’t just for people with metastatic cancers, though many people believe that’s the case. The misconception comes from the belief that trials are a “last resort” meant for people who have tried many other treatments that haven’t worked.

Today, many trials seek newly diagnosed people who have never had treatment in the past. These trials

test medicines as first-line therapies, or the first treatment you receive after diagnosis. Many studies are available for those with metastatic breast cancer, too.

Your oncologist may suggest a clinical trial for you, as Barb Young’s did. But if your doctor doesn’t recommend one or know of any you might be eligible for, you can search for them yourself. Visit clincialtrials.gov, a website run by the National Institutes of Health, to find studies open for enrollment. You can search for trials by breast cancer type, stage, or population needed. If your doctor isn’t aware of open trials or seems unable to help you find one, try accessing listings on advocacy sites like lbbc.org, or visiting clinicaltrials.gov.

If you are from a group underrepresented in trials, such as people under age 40 or over age 65, ethnic minorities or men with breast cancer, you can search for a trial seeking people like you. Living Beyond Breast Cancer also maintains a listing of clinical trials on lbbc.org.

Brooke Cole, 39, of Sanford, Maine, enrolled in a trial she found on clinicaltrials.gov because she wanted to help future generations the way that past generations of trial participants helped her. As a woman with HER2-positive disease, she took trastuzumab (Herceptin), a medicine that wouldn’t exist without successful clinical trials.

Brooke traveled from Maine to Baltimore, Maryland, once every 4 weeks for the first 7 months of a phase II vaccine trial (NCT00524277). She will now go every 6 months for the next 2 – 3 years. Though all medical costs were covered by trial sponsors, travel costs fell to Brooke.

Dr. Wickerham says this is one aspect of trials to be aware of. “It’s important to know the costs of a trial, and that goes beyond the medical expenses to the time you spend and the costs of travel needed.”

New legislation set forth by the Affordable Care Act requires that insurance companies cover the routine costs of participating in approved clinical trials. Many pharmaceutical companies also cover the medical costs if they are sponsoring the trial. The financial impact of joining a trial can be low if you can access one at a facility near your home.

For Brooke, the cost of travel was significant, but her commitment to research kept her going.

“We have to do this kind of research to get it done,” Brooke says. “There have to be people, like me, willing to take part. If you can’t travel and [a trial] is nearby, get involved and enroll. For me, it was an easy decision.”