Cancer has plagued humans since time immemorial, and for nearly as long we have tried to understand and cure it through medical research of varying methods. The evolution of clinical trials, which have become a key component of cancer research, is a complicated tale that highlights the challenges of conducting effective scientific studies. From the first documented trial conducted over 2,500 years ago to James Lind’s eighteenth-century scurvy study, to recent immunotherapy research, clinical trials are the gold standard in rigor and accuracy. Today, clinical trials make the biggest contribution in cancer prevention and treatment breakthroughs.
What is a clinical trial?
The National Cancer Institute defines clinical trials as “research that seeks new ways to improve treatments and the quality of life for people with certain diseases.” This evidence-based approach relies on studies in people to test the safety and effectiveness of medical treatments, devices or strategies that could become tomorrow’s treatment for people with cancer. Research that has evolved from clinical trials also contributes to new ways to prevent and detect the disease.
In essence, people are living longer and can have a better quality of life with or after cancer because of the results of clinical trials.
No matter the design, size or complexity of a clinical trial, they all share the basic principles of a sound scientific experiment:
- A hypothesis. The idea or a new theory that the researcher thinks will happen.
- A trial. The experiment to test the researcher’s hypothesis.
- The results. Did it work? How well and for which people?
Clinical trials follow a study plan, called a protocol, that is developed by the researcher or manufacturer of a drug or device. Before a clinical trial begins, researchers create questions and objectives, followed by other study details, such as:
- Who qualifies to participate in the trial (selection criteria)
- Number of people in a study
- Length of study
- Whether there will be a control group and other ways to limit research bias
- How the medication will be given and what dosage
- What assessments will be conducted, when, and what data will be collected
- How the data will be reviewed and analyzed*
Some cancer clinical trials evaluate therapies that have been around for a long time but can still be improved, such as chemotherapy or hormone therapy. Other trials evaluate new approaches and technologies in surgery, radiation and drug treatments.
Today, many cancer clinical trials are designed to study immunotherapy medications, which stimulate the immune system to fight cancer. Trials might evaluate the safety and efficacy of a medication alone or in combination with other drugs or with radiation or chemotherapy. A trial that evaluates the combination of therapies is known as a combinatorial trial.
Cancer studies require a series of prescribed steps. In clinical research, these are called phases and they determine the evolution of a study. Phase 1 and 2 cancer trials are considered early stages when researchers figure out whether a treatment is safe and effective.
Phases of clinical trials
Phase 1 trials test a new medication, or a combination of medications, for the first time in people. The goals of Phase I trials are to carefully select a dose or schedule of giving the treatment being investigated, and monitoring for safety and tolerability (side effects) of the medications . Researchers closely observe trial participants, evaluating how a medication interacts with the human body, adjusting dosage and monitoring side effects. This can include frequent examinations, blood tests to measure medication levels in the body, and other safety monitoring, like EKGs. The information gathered about a medication’s safety in relation to dosage, as well as signs of effectiveness, help determine its progression to Phase 2. According to the FDA, approximately 70 percent of medications in Phase 1 trials advance to Phase 2.
Phase 2 trials typically include larger numbers of patients in groups with more specific types of cancers. In Phase 2, researchers build on what they learned in the Phase 1 trial, determining if there is enough evidence of the treatment’s effectiveness to continue or expand testing. For example, does the treatment slow tumor growth, and for how long? This phase also helps researchers refine their research methods and design protocols for a Phase 3 trial. Over 30 percent of medications studied in Phase 2 trials advance to Phase 3.
Phase 3 trials are designed to compare a standard treatment against the one being studied in very specific situations. Before a treatment can be approved by the FDA for general clinical use outside of a clinical trial, it must show a significant positive impact on a patient’s life or their cancer. For this reason Phase 3 trials often measure how long it takes before a cancer grows or comes back, also how long a person lives, how long they live free of cancer, or whether there is an improvement in their quality of life.
Phase 0 and phase 4 trials are less common but may be used in some studies. A phase 0 trial is conducted prior to a phase 1 trial to determine if a treatment should be studied. The role of a phase 4 trial is to look at the long-term safety and effectiveness of a treatment that has already been approved by the FDA and is in the market.
What is a randomized trial?
In Phase 3 and some Phase 2 trials, patients are randomly assigned to different groups to receive different treatments. For example, one group may receive a new treatment, the other group may receive a standard treatment. In another example, patients may be randomized to receive a dose or treatment schedule that is being compared to another dose or treatment schedule. A computer is used to assign a person to a group, balancing the distribution of genders, ages or other factors between the two groups to keep them as evenly balanced as possible. This process is called randomization and it is used to help eliminate bias, which can affect the results of the study. Randomly assigning people to treatment groups help the study be more accurate.
“Blinding” a trial is an additional step to help eliminate bias and preserve the accuracy of the study. In a single-blind trial, the participant does not know what group they are in, or the treatment given until the trial is over. In a double-blind trial, neither the participant nor the researcher knows this information (although it is being tracked through a central monitoring system for evaluation of the study results).
Throughout the trial, researchers collect the data and compare the treatments of both groups to see whether one treatment is more effective or has fewer or more side effects than the other.
Why would you choose a clinical trial?
Clinical trial participants are volunteers who decide a study is the right course of action for them. There are clinical trials available for all stages of cancer and by participating you are taking an active role in your own health and helping to advance cancer research. Many clinical trials are designed to be the first treatment a patient receives after their cancer diagnosis. These trials, for example, test a new treatment in addition to the current standard of care treatments. You may also choose to be a part of a clinical trial if there is not a standard treatment available for your type of cancer, or if the standard treatment may be less effective or has severe side effects. A clinical trial may be an option if you have tried all the treatments available but have not had success.
Choosing to participate in a trial is a personal decision. Talk with your physician and family if you are considering a clinical trial.
Clinical trials at Earle A. Chiles Research Institute
At Earle A. Chiles Research Institute, a division of Providence Cancer Institute of Oregon, we conduct a range of investigational and combinatorial clinical studies, focused on:
• Adoptive cellular therapy, a type of immune therapy for people with cancers of the blood, kidney and epithelial tissues lining the pancreas, stomach and other organs
• Cancer genome sequencing for precision treatment and personalized care
• Other new types of immunotherapies for different cancers
• Combining immunotherapy with radiation, surgery and other therapies
• New targeted therapies, designed to specifically treat cancers with certain mutations in the DNA of the cancers that may make them more sensitive to new treatments
• Side-effects of chemotherapy, radiation, or surgery, and how to improve quality of life for cancer patients and survivors
Our researchers and physicians work together to bring new, effective and safe cancer treatments directly from our onsite lab to our patients. At any given time, we have over 400 clinical trials in progress, including ones initiated by our own researchers. We have broadened opportunities for our patients by participating in cooperative trials with researchers and organizations outside of Providence.
If you are interested in participating in a clinical trial, visit our website to see all studies in all cancer types at Providence Cancer Institute.
*Source: U.S. Food and Drug Administration, Basics about clinical trials