What are the Phases of Clinical Trials?

MD Anderson Cancer Center
Date: October 2012

Patients who participate in clinical trials receive drugs or procedures that first have been researched in successful laboratory and/or animal studies.  Studies then go through several phases of testing in people before the U.S. Food and Drug Administration, or F.D.A., approves them as safe and standard treatments.  Some clinical trials also study new ways of using drugs or procedures that have already received approval by the F.D.A.  Clinical trials are conducted in three or four steps that are known as Phases.  The goal of a Phase I clinical trial is to find the safest maximum dose that the patient can receive without experiencing excessive side effects.  This type of trial can also determine the best way to give the drug, for example, either by mouth or intravenously through a vein.  Many of the drugs in Phase I trials are being tested for the first time in people.  In Phase I trials, drugs often are tested in multiple kinds of cancer at the same time.

A Phase II clinical trial is a study to determine the effectiveness of a treatment, how well it works to fight a certain type of cancer.  Less than 100 people usually participate in a Phase II trial. 

Patient 1
Robert Holman: So I came to MD Anderson, and they examined me and everything, and then they approached me about medical trials, and they laid it all out for me.  That I could go with regular radiation and chemo, and, you know, try that, or I could go with clinical trial.

Are you having any pain or -

Patient 1

The Phase II clinical trial offered to Robert Holman was designed to test the effectiveness of adding a new drug to standard chemotherapy. 

Patient 1
Robert Holman: Since my life was in the balance, that really wasn't a big question.  So I said yes.

Doctor 1
The objective of a Phase I trial is to try to determine the appropriate dose in human beings.  Once you know the appropriate dose and the toxicity profile, then you go to the Phase II setting where you ask the question is it active in sarcomas, breast cancer, lung cancer, colon cancer, and the like.  Once you prove that it has this level of activity, and, yes, it is encouraging, then you say in a Phase III setting or then you ask the question how does it compares to the current standard of care.

A Phase III trial seeks to find out whether a new treatment is better than the standard treatment.  These studies may include hundreds even thousands of patients.  The trials often are randomized, meaning the patients have an equal chance of being assigned to a group receiving the new treatment or to a group receiving the existing standard treatment.  Neither the patient nor the doctor can choose which group the patient is assigned to.  Regardless of which group a patient is assigned to, he or she will receive either the best standard treatment available or the new treatment that researchers believe is as good as or perhaps better than the standard treatment.  A protocol is a detailed plan that explains what will help in a clinical trial.  Sue Schwartz's protocol called for testing a new chemotherapy treatment followed by surgery and six weeks of radiation therapy.

Patient 2
Sue Schwartz: MD Anderson assured me that the protocol was not a lesser treatment.  It, in fact, they weren't sure which one was better, but that they weren't offering an inferior, and they assured me that they never do that.  That all of their protocols are between equals or something that they think will be better.  Never between something that they think will be worse.  So that gave me a great deal of comfort. 

Phase IV clinical trials are studies that gather additional information about treatments that already have been approved for use in patients by the F.D.A. 

Doctor 2
Sometimes some effect is so rare that even if you give the drug to several hundred people you don't see it, but when you start giving it to thousands of people, you begin to see it, and that's the importance of Phase IV trials, and they're very important.