What are the Phases of Clinical Trials?

After promising treatments are explored in animal and/or laboratory studies, researchers perform clinical trials. Once the drug, device or procedure enters the clinical trials process, it must go through several phases:

• Phase I trials determine the safety of a new treatment
• Phase II trials determine whether a certain kind of cancer responds to a new treatment
• Phase III trials study whether a new treatment is better than standard treatment
• Phase IV trials find more information about a new treatment that has been already approved for use in patients

Phase I Trials – Determine if a new treatment is safe and effective in humans. Doctors also find the best way to give the treatment.

The goal of a Phase I trial is to:

• Find out if a new treatment is safe
• Find the best way to give the new treatment, such as by mouth or by vein
• See if the treatment prevents the cancer from growing

Phase I trials usually include 15 to 30 patients who are divided into small groups. These groups are called cohorts. The first cohort receives a low dose of the new drug. Doctors may collect blood or urine samples to measure drug levels in the patients.

If the first cohort does not have any severe side effects, then a new cohort receives a higher dose of the same drug. The dose increases with each new cohort until the doctors find the safest effective dose. With each increasing dose, doctors test each patient to see if he or she is responding to the treatment.

If the doctors find that the treatment is safe, then it will move forward to be studied in a Phase II trial.

The Clinical Center for Targeted Therapy provides many of M. D. Anderson’s Phase I clinical trials. Ask your doctor to refer you to this center if you are interested in joining a Phase I clinical trial.

Phase II Trials – Determine whether the new treatment works

The main goal of a Phase II trial is to examine how well the new treatment works to fight a certain kind of cancer. Less than 100 patients usually participate in a Phase II trial. Patients who volunteer for a Phase II trial may have been treated with chemotherapy, biotherapy, surgery or radiation and still need further treatment.

In addition to evaluating how well the treatment works against the cancer, doctors continue to monitor side effects. Since more patients participate in Phase II studies, some of them may experience side effects that patients in the Phase I clinical trial did not have.

If the new treatment seems to be effective against cancer in a certain percentage of patients, researchers may consider it successful enough to continue study in a Phase III clinical trial.

Phase III Trials – Study whether the new treatment is better than standard treatment

The goal of a Phase III trial is to compare the new treatment with the standard treatment. Researchers track whether a new treatment is better than, the same as, or less effective than the standard treatment.

Phase III trials may include hundreds to thousands of patients around the country or world. In general, each patient enrolled in a Phase III clinical trial has an equal chance of participating in one of two or more arms (groups) of the study. In a clinical trial with two arms:

• The control group receives the standard treatment
• The investigational or experimental group receives the new treatment being tested

Randomization is the process of assigning participants to groups. Randomization helps avoid bias in the clinical trial. Bias occurs when human choices or other factors not related to the treatment being tested change a study’s results.

Neither the patient nor the doctor can choose whether the patient is in the control group or the experimental group. Regardless of which group a patient is assigned to, either he or she will receive the best standard treatment available or the new treatment that researchers believe is as good as, or better than, the standard treatment.

Single Blind Versus Double Blind Trials

• Single blind studies: patients do not know whether they are in the experimental or control group
• Double blind studies: neither the patients nor the researchers know which patients are in each group (although this information is recorded and on file if needed)

FDA Approval

The role of the U.S. Food and Drug Administration (FDA) is to make sure medical treatments are safe and effective for people to use. Researchers submit their clinical trial results to the FDA, and based on the information, the FDA may approve the drug or treatment. Then it becomes available to all patients and sometimes becomes the new standard treatment.

Phase IV Trials – Find more information about the new treatment

Phase IV clinical trials are not as common as Phase I, Phase II and Phase III trials. In Phase IV trials, researchers study drugs and/or treatments that have already received FDA approval. The goal of Phase IV trials is to study how safe and effective a drug or procedure is over time.