Phases of Clinical Trials

Approved by the Cancer.Net Editorial Board, 12/2015

Preclinical research

Before conducting any clinical trials in people, doctors must prove that their explanation on how the treatment works is right. This explanation is called the research hypothesis. The research community calls this stage, which takes place in a laboratory, preclinical research. It often takes years for doctors to turn information from this stage into a new treatment. After early clinical research suggests that a new drug may work, it is tested in laboratory animals. Only then, would doctors propose clinical trials in people.

In some cases, the research suggests that the treatment might be an effective cancer treatment. If so, the clinical trial sponsor files an Investigational New Drug (IND) application. The application asks the U.S. Food and Drug Administration (FDA) for permission to study the treatment in people. If the FDA approves the application, the sponsor can move to the next research step. This includes studies to find out more about the treatment.

Clinical Research

Doctors generally do clinical research in three distinct phases:

  • Phase I

  • Phase II

  • Phase III

Each phase describes the information that the doctors collect about a new treatment in a clinical trial, including:

  • The dose

  • Safety

  • How well the treatment works

Phase I clinical trials

A phase I clinical trial tries to show that people can safely use a new drug or treatment. Doctors collect data on the dose, timing, and treatment safety. At this point, doctors have already shown the drug or treatment to be safe for animals. People who join phase I clinical trials are often the first to get a new therapy or combination of therapies.

In phase I clinical trials, doctors slowly increase the dose of the drug being studied. The goal is to find the dose that works best without causing severe side effects. The research community calls this process dose escalation. The first people in the trial get a small dose of the drug. If there are no or few side effects, the next participants get higher drug amounts. Doctors keep testing until they find the highest dose with the least side effects.

Sometimes, the doctors need to find the best way to give the new treatment. For example, this could be by mouth or through a vein. The doctors also collect data on:

  • How the body absorbs the drug

  • How the body uses the drug

  • How the drug spreads in the body

Phase I clinical trials often last several months to a year. They usually have only 10 to 30 people. Doctors offer treatment in phase I clinical trials to people whose cancers won’t respond to standard treatments. Doctors don’t design these trials to test how well a treatment or combination of treatments works. However, the treatment given during this phase sometimes may help to slow or stop the growth of a person’s cancer.

Doctors tested all treatments that are available now in people during phase I clinical trials.

Phase II clinical trials

Phase II clinical trials give doctors more information about the treatment’s safety and how well it works. These trials also look at whether the new treatment works for a specific cancer. Doctors may measure the tumor size or analyze blood test results to learn if the treatment is working.

Phase II clinical trials take about 2 years. They usually have 30 to 120 people. Sometimes phase II clinical trials will assign different people to several possible treatments. This may include standard treatment compared with standard treatment plus the treatment being studied. Or, people may be assigned to receive different doses of the treatment. Researchers call this a randomized phase II trial. Such a trial may have up to several hundred patients.  

Doctors need to show that the new treatment is likely to work and that it’s as safe as standard treatment. If it is, research can move to phase III clinical trials.

Phase III clinical trials

Phase III clinical trials start with a new treatment that’s worked well in a small number of patients with a certain disease. Doctors compare the treatment with the standard of care for that disease. They do so by gathering data from large numbers of patients, typically more than 300, and sometimes many thousands of people. The goal is to find out if the new treatment is better than standard treatment and/or with fewer side effects.

Phase III clinical trials are usually randomized. That means doctors don’t choose which person gets the new treatment or the current standard treatment. In this phase, doctors compare 2 or more treatment options.

These trials include patients of different ages and ethnicities, and both genders. This helps doctors apply the results to a large number of people. Phase III clinical trials often take doctors many years to finish.

Once the research shows that the treatment works well against a specific cancer, doctors can apply for FDA approval. If data from the clinical trials meet FDA standards, the FDA approves the treatment for a specific use.

Sometimes doctors prescribe a drug for a use not specified by the FDA. This may be because studies in peer-reviewed journals show that the treatment works for other diseases, conditions, or symptoms. Drug companies call this "off-label" use. However, such “off-label” use of drugs is not always covered by insurance companies.

Learn more about the drug development and approval process.

More Information

Finding a Clinical Trial

Clinical Trials

PRE-ACT: Preparatory Education About Clinical Trials

Additional Resource