Clinical Trial Phases
New interventions are often studied in a stepwise fashion, with each step representing
a different “phase” in the clinical research process. The following phases are used
for cancer treatment trials:
These trials represent the earliest step in testing new treatments in humans. In
a phase 0 trial, a very small dose of a chemical or biologic agent is given to a
small number of people (approximately 10-15) to gather preliminary information about
how the agent is processed by the body (pharmacokinetics) and how the agent affects
the body (pharmacodynamics). Because the agents are given in such small amounts,
no information is obtained about their safety or effectiveness in treating cancer.
Phase 0 trials are also called micro-dosing studies, exploratory Investigational
New Drug (IND) trials, or early phase I trials. The people who take part in these
trials usually have advanced disease, and no known, effective treatment options
are available to them.
Phase I (also called phase 1)
These trials are conducted mainly to evaluate the safety of chemical or biologic
agents or other types of interventions (e.g., a new radiation therapy technique).
They help determine the maximum dose that can be given safely (also known as the
maximum tolerated dose) and whether an intervention causes harmful side effects.
Phase I trials enroll small numbers of people (20 or more) who have advanced cancer
that cannot be treated effectively with standard (usual) treatments or for which
no standard treatment exists. Although evaluating the effectiveness of interventions
is not a primary goal of these trials, doctors do look for evidence that the interventions
might be useful as treatments.
Phase II (also called phase 2)
These trials test the effectiveness of interventions in people who have a specific
type of cancer or related cancers. They also continue to look at the safety of interventions.
Phase II trials usually enroll fewer than 100 people but may include as many as
300. The people who participate in phase II trials may or may not have been treated
previously with standard therapy for their type of cancer. If a person has been
treated previously, their eligibility to participate in a specific trial may depend
on the type and amount of prior treatment they received. Although phase II trials
can give some indication of whether or not an intervention works, they are almost
never designed to show whether an intervention is better than standard therapy.
Phase III (also called phase 3)
These trials compare the effectiveness of a new intervention, or new use of an existing
intervention, with the current standard of care (usual treatment) for a particular
type of cancer. Phase III trials also examine how the side effects of the new intervention
compare with those of the usual treatment. If the new intervention is more effective
than the usual treatment and/or is easier to tolerate, it may become the new standard
Phase III trials usually involve large groups of people (100 to several thousand),
who are randomly assigned to one of two treatment groups, or “trial arms”: 1) a
control group, in which everyone in the group receives usual treatment for their
type of cancer, or 2) an investigational or experimental group, in which everyone
in the group receives the new intervention or new use of an existing intervention.
The trial participants are assigned to their individual groups by random assignment,
or randomization. Randomization helps ensure that the groups have similar characteristics.
This balance is necessary so the researchers can have confidence that any differences
they observe in how the two groups respond to the treatments they receive are due
to the treatments and not to other differences between the groups.
Randomization is usually done by a computer program to ensure that human choices
do not influence the assignment to groups. The trial participants cannot request
to be in a particular group, and the researchers cannot influence how people are
assigned to the groups. Usually, neither the participants nor their doctors know
what treatment the participants are receiving.
People who participate in phase III trials may or may not have been treated previously.
If they have been treated previously, their eligibility to participate in a specific
trial may depend on the type and the amount of prior treatment they received.
In most cases, an intervention will move into phase III testing only after it has
shown promise in phase I and phase II trials.
Phase IV (also called phase 4)
These trials further evaluate the effectiveness and long-term safety of drugs or
other interventions. They usually take place after a drug or intervention has been
approved by the FDA for standard use. Several hundred to several thousand people
may take part in a phase IV trial. These trials are also known as post-marketing
surveillance trials. They are generally sponsored by drug companies.
Sometimes clinical trial phases may be combined (e.g., phase I/II or phase II/III
trials) to minimize the risks to participants and/or to allow faster development
of a new intervention. Although treatment trials are always assigned a phase, other
clinical trials (e.g., screening, prevention, diagnostic, and quality-of-life trials)
may not be labeled this way.
Adapted from the National Cancer Institute's PDQ Database: http://www.cancer.gov/cancertopics/factsheet/Information/clinical-trials.
(Accessed December 2010)