Phases of Clinical Trials

Dr. Skip Burris of the Sarah Cannon Research Institute explains how the phases of clinical trials work.

Q: Welcome to Understanding Cancer.  Today we’re visiting with Dr. Skip Burris, who is the director of drug development at the Sarah Cannon Research Institute in Nashville, Tennessee.  Dr. Burris has extensive experience in new drug development as well as clinical trials in general, with a focus on oncology.  Welcome.

A: Thank you.

Q: One thing I think that confuses patients is there are several phases of clinical trials.  You hear about Phase I, Phase II, Phase III, Phase IV clinical trials.  Could you sort of concisely walk us through the difference between a Phase I, II and III clinical trial?

A: So a Phase I trial is essentially for patients whose…their tumors have not responded to standard therapy.  So these patients have been through traditional treatment and their tumors haven’t shrunk or gone away.  So their doctor considers them an appropriate candidate and they’re motivated to look at additional treatment.

So these are brand new drugs, different mechanisms of killing cancer cells, and the purpose of the trial is to really, to look at what’s the safest route and what’s the most efficacious route to give the drug, so looking at the safety and the scheduling of the agent.  But in all these trials, the bottom line is can we make the patient’s tumor shrink?  Can we make patients live longer with a better quality of life?

Once a drug is determined to be safe and we have a good idea of the schedule on which it should be given, then the drug moves into a Phase II trial, and this tends to be a much more uniform group of patients.  A Phase II trial will be 40 to 60 patients all with the same type of breast cancer, all the same type of colon cancer or lung cancer, based on where we think the drug might work.

And then if the drug looks sufficiently active, if we see a certain number of tumors shrink, if we get a feeling that the drug might work, then the drug moves into Phase III studies.  And Phase III studies are when you begin to add these drugs to standard of care regimens.  So you’ve got a good standard of care therapy and then half the patients will get the new drug in addition, and half the patients will just get the standard of care treatment.  And the comparison in that Phase III trial is what usually leads to FDA approval and the drugs becoming available to patients throughout the country.

Q: So the Phase III trial is really where the patient is getting randomized, right, and that’s something that concerns patients.

A: It does concern patients.  It’s interesting, when you start to think about it and you think Phase I really early, really new, do I want to participate.  But as you suggest, in a Phase I trial, everybody’s getting the study medication, so there’s no randomization, there’s no placebo; everybody gets the real drug.  When we go to Phase II, it tends to be the same thing.  Now it’s a much more uniform group of patients, but everybody is getting the drug and everybody is getting it on the same schedule, and the patients look much more similar.

Phase III means that the drug has looked active enough and has looked safe enough that now we want to see if it will add to or be better than standard of care.  So now the drug’s been through four or five years of clinical development, but now it becomes the part that you can get a little scary with.  You might not get the new therapy in the randomization, often left up to a computer.

So…and that’s the place where sometimes the placebo comes into play, so a sugar pill or a dummy injection, and that’s a situation where you just have to remember everybody is getting standard of care.  This is what you would have gotten off trial.  And then half the patients are going to get the new medicine and half the patients are not.

Q: One question I often get is in a Phase III trial, well, why can’t I just get the experimental treatment?  Why do I have to  participate in a Phase III trial?

A: And I think that we’ve learned through the years that sometimes we get surprised in a Phase III trial.  So we’ve done the best work we can in Phase I, II to decide what’s the best dose, what’s the best schedule for the drug to be delivered on, and how we should give it to patients, and then we get an idea of how well it works.

And then we go to a Phase III trial where now hundreds or maybe even thousands of patients will be treated, and we will look at it, and you looked at a body of a thousand patients, you might find out that four or 5% of the time you’re having a side effect that isn’t seen in the other group.  So relatively low percentages of events, but enough that it might be a concern once these drugs are out there.

You have to remember, for example, that you’re going to have almost 200,000 women diagnosed with breast cancer in the United States this year, so when a new therapy comes out for breast cancer, the numbers aren’t going to affect, you know, 40 patients or 60 patients like the Phase II trial, it’s going to affect thousands of patients.  And it’s only in those larger trials where we really see the relative benefits and the relative risks for taking the new therapy.

Q: Well, Skip, thank you for your time today, and we really look forward to having you back.

A: Thank you.

[End of recording.]