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Phases of clinical trials

Clinical trials for new treatments are always tested through several steps, called phases. Other types of trials, such as screening and early detection, diagnostic or supportive care studies, do not necessarily have phases. In a treatment trial, each phase is designed to answer specific research questions. A new approach to cancer treatment can only progress to the next phase after it is shown to be safe and effective. This is why it often takes a long time for an experimental treatment to be approved as a cancer treatment. There are up to 5 phases involved in a clinical trial: phases 0, I, II, III and IV.

Preclinical trials

Scientists test new ideas in the laboratory first, to see the effects on animals or on human cells, before testing it with humans. It is difficult to know what effect a new treatment will actually have when it is used with humans. The effects may not be the same as they were in the laboratory or animal studies.

Phase 0

Sometimes a phase 0 trial is conducted before a phase I trial. Phase 0 trials use a very small dose of a drug to study the effects in a small group of people (about 10–15). These trials are used to gather information about how the drug is used by and affects the human body. Researchers may need blood tests or biopsiesbiopsiesThe removal of cells or tissues for examination under a microscope. of the tumour. Phase 0 studies are not used to gather information about the safety of the drug or its effectiveness in treating cancer. People who take part in phase 0 studies usually have advanced disease and do not have an effective, known treatment option.

Phase I

Phase I trials look at how safe a treatment is and try to determine the best dose. A phase I trial tries to find out:

  • how the new treatment should be given (such as by mouth or injection) and how often
  • the safest dosage and the highest dose a person can tolerate (maximum tolerated dose)
    • Participants are divided into groups called cohorts.
    • Each cohort is made up of 2–6 people.
    • The first cohort is given a dose that is thought to be safe (based on the results of animal studies). Then the dose is gradually increased in the other cohorts. This increase in dose is called dose escalation.
  • what effect the drug or therapy has on the body
  • what side effects people taking the drug or treatment experience

A phase I trial is often the first time a new drug, combination of drugs or therapy is tested on humans, so these trials may involve more risk compared to phase II or III trials. For this reason, phase I trials usually involve only a small number of people with cancer (about 15–30) who are not getting better with standard treatment. Phase I trials are not always specific to one type of cancer and may be used in people with different types of cancer.

Phase I trials may also test an already approved drug or therapy to try to improve its effectiveness or see if it can be used in a different way. For example, a phase I trial may test a drug or therapy that is already used for another disease or type of cancer.

Most phase I studies in children are done once phase I of the adult trial has been completed or is near completion. They use the same drug or treatment as the adult trial. However, children are often started on a lower dose than that given to adults.

The dose and schedule that researchers find most effective with tolerable and reversible side effects in a phase I trial is used to determine the dose and schedule of a phase II trial.

Phase II

Phase II trials test whether a drug or other treatment is effective against a specific type of cancer based on the dose and schedule determined to be safe in a phase I trial. Phase II trials may also compare different schedules of giving the treatment. Researchers study a drug or treatment in a relatively small group of people (usually less than 100) with one type of cancer. Most participants in phase II trials have not responded well to standard treatment or do not have a standard treatment available to them.

Phase II trials:

  • try to get a better idea of how effective a treatment is for a certain type of cancer
  • continue to evaluate how safe the drug is and what effect it has on the body

Phase III

A phase III trial provides a detailed evaluation of a promising new treatment identified during a phase II trial. It compares the new treatment to the best current standard of cancer treatment. Researchers may test a drug alone or in combination with another drug or form of treatment. Phase III trials usually involve a large number of people (hundreds to thousands) at several different locations. People who participate in phase III trials may not have received any previous treatment.

A phase III trial tries to:

  • find out whether the treatment being tested is better, as good as or worse than the standard treatment
    • This includes evaluating quality of life and survival.
  • compare side effects of the new treatment and the standard treatment

Phase III trials often depend on a process called randomization. This means that participants are selected by chance and put into 1 of 2 groups. An experimental group receives the new treatment being tested, while the control group receives the standard treatment. Some trials may involve more than 2 groups of participants. Randomization helps make sure the study results are accurate.

If the results of a phase III trial show that the experimental treatment is better than the standard treatment, the experimental treatment may move forward to become the new standard treatment.

Phase IV

Phase IV trials gather more information about the possible risks and benefits of a drug that didn’t show up in earlier testing. Researchers look into risks and benefits that could be associated with long-term effects after a drug or treatment has been approved for clinical use. In this phase, researchers continue to follow participants who have completed phase III trials. Not all new treatments will enter into phase IV studies.

Approving a new drug or treatment

After clinical trials show that a new drug or treatment for cancer is safe and effective, it is submitted to Health Canada for approval. Once approved, doctors can then recommend this treatment to people with cancer.

It often takes more than 10 years for a new drug or treatment to go from preclinical trials, through clinical trials, to the approval process before it is available as a standard treatment to people with cancer.

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