Clinical Trials: What They Are, Who Participates and Why It Matters

Changes to standard treatment in the last 50 years have dramatically changed breast cancer care.

“When I started medical school in the early 1970s, the treatment of breast cancer was simple: Everybody had a radical mastectomy,” says Lawrence Wickerham, MD, the deputy chair of NRG Oncology, a nonprofit research organization. Radical mastectomy, a surgery that was common for nearly 100 years, cut away the entire breast, the chest muscles underneath and all the nearby lymph nodes.

“Today, our [medical] residents have never seen a radical mastectomy,” Dr. Wickerham says. “They’re just not done.”

Surgeries that remove less tissue and tailored medicines for particular types of breast cancer have replaced radical mastectomies. And like all treatments, they were first proved safe and effective in clinical trials.

Clinical trials are studies carried out in people to learn more about diseases, like breast cancer, and their treatments. Clinical trials for breast cancer often explore

• new treatments
• new combinations of existing treatments
• the order treatments are given
• the dose and timing of treatment
• how a treatment is given (by mouth or by vein, for example)
• quality of life

About Clinical Trials

Many people worry about getting untested treatments. But trials come in different types and phases designed to identify safety issues and protect participants as much as possible.

For treatment trials, researchers must first find strong evidence, through lab experiments, that the treatment might work. Then they can run a phase I clinical trial in people. Phase I trials recruit up to 30 people and look for unexpected side effects. In phase II, researchers measure how well the treatment works in a larger group, usually fewer than 100 people, while still tracking side effects. Phase III treatment trials recruit hundreds or thousands of participants. They compare the study treatment to a standard treatment, and are often the last step before approval from the U.S. Food and Drug Administration.

Trials can be randomized, meaning a computer assigns people to a group getting standard therapy, called the control arm, or one getting the study treatment. Randomization increases accuracy by spreading other factors that could affect a person’s health evenly among the groups.

Trials also may be blinded, meaning you and your doctor may not know whether you are getting the study or the standard treatment. In a double-blind study neither you nor the healthcare team knows. In a single-blind study, the doctor knows but you do not. In an open-label study, both you and your care team know what you are taking.

Not all research assigns and compares treatments. Observational studies collect data about people and their health by sending them surveys or looking at medical records. Other clinical trials study medical tests, fitness programs, diets, complementary therapies, and more.

Kathy Conway, 60, of Wilmette, Illinois, was diagnosed in 2009 with stage III hormone receptor-positive breast cancer. Her doctor recommended a clinical trial. She agreed to a phase III double-blind, randomized trial testing how a newer medicine worked in breast cancers with a high risk of metastasizing.

For her trial, Kathy got standard chemotherapy by vein. Then she was given another medicine: She did not know at the time if it was the study medicine or a placebo, something that looks like the treatment but has no active medicine. She felt disappointed when she learned she received the placebo, but she still sees the trial as a positive experience. She got the treatment she needed and helped researchers better understand the study medicine. She went on to participate in other studies, too.

In all trials, researchers closely watch the health of participants. If you start experiencing treatment side effects, the study doctors may adjust your dose, or if the effects are too much, suggest you discontinue the study treatment. Researchers will still be able to use data from your participation even if you and your doctors decide you should stop taking the medicine, but you have the right at any time to remove yourself and your data from the study if you wish.

On Getting (and not Getting) Participants

A big challenge for researchers is finding enough people to participate in clinical trials. Only 3 percent of adults with a cancer diagnosis participate in clinical trials. But getting meaningful results requires a large number of participants. Trials also need people with diverse backgrounds, since factors like ethnicity, weight and income can affect results.

Far fewer people with lower incomes enroll than those with higher incomes. Racial and ethnic minority women are also less likely to participate. There are many possible reasons, Dr. Wickerham says, from bad past experiences to practical challenges such as paying for childcare or transportation to get to appointments.

Many trials are run by large research hospitals in major cities. This puts trials out of reach to some in rural areas and smaller towns or cities.

“The problem still exists but we improved upon things,” Dr. Wickerham says. “They’re still done in those places but … now patients can enter [some] clinical trials in their communities.”

As a patient, finding the right trial can be a challenge. Clinical trials can have requirements related to your age, menopausal status, diagnosis, genetic mutations, past treatments and other health conditions.

Only 3 percent of adults with a cancer diagnosis participate in clinical trials. But getting meaningful results requires a large number of participants. Trials also need people with diverse backgrounds, since factors like ethnicity, weight and income can affect results.

Other challenges include access and costs. You may be able to keep your current healthcare team, or you may have to see doctors at a different location. Trials may require extra time or visits. Some costs may be covered by the trial. The research team can tell you what’s needed.

Most people who enroll in clinical trials learn about them from their doctor, but Elly Cohen, PhD, program director of BreastCancerTrials.org, says you can take action if you are interested. Start by telling your doctor, so he or she can see if any are available for you. Look at resources like BreastCancerTrials.org, which allows you to find trials that match your situation, or ClinicalTrials.gov, a database of most open trials.

Easing Concerns

Another obstacle: earning people’s trust in the process. This is especially true for African-Americans and other minority groups who were taken advantage of in past clinical trials.

In the Tuskegee Syphilis Study, hundreds of African-American men were lied to over 40 years, from the 1930s to the 1970s. Of the 600 men enrolled, 399 had syphilis. The men were told they were being treated for “bad blood” but were denied proper treatment. By the time the trial was brought to people’s attention in 1972, seven men had died of syphilis, and many more suffered and died of issues linked to the disease.

Sonnetta Jones, 41, of New Brunswick, New Jersey, was diagnosed with stage II triple-negative breast cancer in May 2013. Her doctor suggested a clinical trial for a medicine showing promise for early-stage breast cancers like Sonnetta’s. But Sonnetta was reluctant.

“I remember reading about [Tuskegee]. I was so angry. I was like ‘How can we test [on] these people and not have them be aware of the dangers?’” Sonnetta says. She worried she would receive a placebo instead of active treatment.

Concern about getting a placebo is common, according to Dr. Cohen, and springs from people not knowing today’s trial process. People in the control arm, the group that does not get the treatment under study, may be given a placebo. But it is always in addition to a standard treatment. Your treatment with the placebo must be as good as the treatment you can expect outside the trial.

To put her mind at ease, Sonnetta’s doctors brought in the study researchers to explain it and answer her questions. They went over the safety measures and her rights as a participant. The discussion eased Sonnetta’s concerns, but it wasn’t until she later read an article they provided that she decided to enter the trial.

In the article, “they were speaking about African-Americans and [how] they need more of us to be involved in clinical trials because they need to figure out why cancer is so aggressive in our bodies,” Sonnetta says.

Studies show breast cancer is more likely to be diagnosed at a later stage and more likely to be triple-negative in African-American women, Dr. Cohen says.

For Sonnetta the article was a sign that she should join the trial, a decision she is happy with after treatment with the trial medicine shrank the tumor before she had a lumpectomy.

Clinical trials are now designed and reviewed by experts before they enroll participants. They must be approved by institutional review boards, made up of doctors and people outside medicine, often administrators, religious leaders, ethicists or lawyers.

“Everybody wants the best possible care for themselves, or their friends or family, and I often tell them clinical trials fall into that category,” Dr. Wickerham says.

Dr. Wickerham points to today’s institutional standards and oversight. Clinical trials are now designed and reviewed by experts before they enroll participants. They must be approved by institutional review boards, made up of doctors and people outside medicine, often administrators, religious leaders, ethicists or lawyers. Their role is to oversee the study in the interest of its participants.

And before enrolling, you must give informed consent. This means researchers must talk to you about the details of the trial, including its benefits and risks, any financial costs, and how it will be structured and monitored. Once enrolled in the study, you can choose to leave it at any time.

Targeted Therapies and New Formats for Trials

A recent trend in clinical trials is to focus on characteristics of the person or the cancer, according to Dr. Wickerham. A study may focus on postmenopausal women, HER2-positive breast cancers, or gene mutations.

“The benefits of the targeted therapies [is that] they have the promise of being far more effective [in certain people],” Dr. Wickerham says. But recruiting enough people with a specific feature can be difficult.

Researchers have responded by using new formats. Umbrella trials focus on breast cancers with unique features, such as certain genetic mutations. These trials have multiple arms, each testing a different treatment. It allows researchers to test more than one treatment at a time.

In basket trials, people with any type of cancer that shares a certain feature or behavior are enrolled in one trial, no matter where the cancer started. People with breast cancer may be enrolled in the same trial as people with lung or colorectal cancer, all testing the same treatment. This type of trial resulted in pembrolizumab (Keytruda) becoming the first medicine approved based on the way it treats a genetic feature of cancer, not on where the cancer is located.

Benefits of Clinical Trials

The benefits of clinical trials to you and to cancer research can be significant. Pat Hazebrouck, 59, from Millville, Massachusetts, was diagnosed with metastatic breast cancer in 2015. She was first treated with chemotherapy pills, but by summer 2016 the cancer had grown. Hoping to delay the move to chemotherapy by vein, her doctor suggested a phase I clinical trial exploring another type of chemotherapy and a medicine called a cyclin-dependent kinase inhibitor, both taken as pills.

As with any cancer treatment, these new medicines had side effects. Doctors lowered the dose for one medicine because it affected Pat’s kidneys. After that, she had few other side effects. She continued to work part-time as a nurse throughout the trial, which she stayed in for just over a year before the cancer grew again.

Not all medicines in clinical trials succeed. The trial may find the new medicine does no better than current medicines. Even if the medicine meets goals set out by the researcher, it may not work for you. Your healthcare team will watch and change your treatment if the cancer does not respond. If the treatment does not work in many people or causes severe side effects, the review board will stop the trial.

Pat was happy to put off IV chemotherapy for another year. She now receives chemotherapy by vein, but plans to enroll in other clinical trials when she finds the right one.

What most excites Pat is helping researchers learn more about breast cancer and possible new treatments.