Watch the Cancer.Net Video: Phases of a Cancer Clinical Trial, with Nicholas Petrelli, MD [2], adapted from this content.

Key Messages:

• Clinical trials are made up of distinct parts called phases.
• Phase I clinical trials are used to show that a new treatment is safe for a small group of people.
• Phase II clinical trials provide more information about the safety of the new treatment and how well it works to treat cancer.
• Phase III clinical trials compare the new treatment with the standard treatment in a large group of people.

Doctors and researchers conduct clinical research in phases. Each phase of a clinical trial is designed to provide different information about the new treatment, such as the dose, safety, and how well it works. The phases are described as I, II, and III.

Preclinical research

Before a new treatment can be given to patients, the underlying research hypothesis (the explanation for how the new treatment works) must be proven in a laboratory. This stage is called preclinical research, and it often takes years to turn this knowledge into a new treatment.

If the laboratory research suggests that the treatment might be an effective cancer treatment, the sponsor of the clinical trial files an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) requesting permission to study the treatment in people. If the IND application is approved, researchers can move on to the next step of research, which includes studies to find out more about the treatment.

Phase I clinical trials

The goal of a phase I clinical trial is to prove that a new drug or treatment, which has proven to be safe for use in animals, may also be given safely to people. Doctors collect data on the dose, timing, and safety of the treatment. People who participate in phase I clinical trials are often the first to receive a new therapy or a new combination of therapies.

In phase I clinical trials, the dose of the drug being studied is gradually increased to find the dose that works best without causing severe side effects. This process is called dose escalation. The first participants are given a small dose of the drug. If there are no or few side effects, the next participants are given higher amounts of the drug until the doctors find the highest dose with the fewest side effects. Sometimes, the doctors need to find out the best way to give the new treatment, such as by mouth or through a vein. In addition, the doctors collect data on how the drug is absorbed, processed, and spread throughout the body.

Phase I clinical trials generally last several months to a year and involve a very small number of people, usually no more than 10 to 20. People whose cancers have not responded to previous treatment are often offered treatment in phase I clinical trials. Although phase I clinical trials are not designed to test how well a treatment or combination of treatments work, sometimes a person's cancer will respond to investigational treatments in this phase.

Phase II clinical trials

Phase II clinical trials are designed to provide more detailed information about the safety of the treatment, in addition to evaluating how well it works. These clinical trials focus on finding out whether the new treatment works for a specific cancer, which may be measured by a decrease in tumor size or through blood tests. Phase II clinical trials take about two years to complete and usually involve about 20 to 40 people. The new treatment needs to work as well or better than the standard treatment for it to be tested in Phase III clinical trials.

Phase III clinical trials

The goal of phase III clinical trials is to take a new treatment that has shown promising results when used for a small number of patients with a particular disease and compare it with the current standard of care for that specific disease. In this phase, data are gathered from large numbers of patients to find out whether the new treatment is more effective and possibly has fewer side effects than the current standard treatment. Phase III clinical trials are usually randomized, meaning that patients receive either the investigational treatment or the standard treatment in a non-ordered way. Although phase III clinical trials focus on patients with a specific disease, they typically include patients of various ages, ethnicities, and both genders so that the results may be applicable to a large number of people. The number of people enrolled in a phase III clinical trial can range from the hundreds to the thousands, and these clinical trials take many years to complete.

Once a drug has been proven successful in a phase III clinical trial, the researchers can submit an application for FDA approval. If data from the clinical trials meet the FDA's standards, the treatment is approved for a specific use. However, doctors sometimes prescribe a drug for a use not specified by the FDA, but rather based on studies published in peer-reviewed journals showing that the treatment works for other diseases, conditions, or symptoms; this is called "off-label" use. Learn more about the drug development and approval process [3].

More Information

Finding a Clinical Trial [4]

Clinical Trials [5]